Journal articles: 'C-terminal domain of perlecan'

1

Zoeller, Jason J., Angela McQuillan, John Whitelock, Shiu-Ying Ho, and Renato V. Iozzo. "A central function for perlecan in skeletal muscle and cardiovascular development." Journal of Cell Biology 181, no. 2 (April 21, 2008): 381–94. http://dx.doi.org/10.1083/jcb.200708022.

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Perlecan's developmental functions are difficult to dissect in placental animals because perlecan disruption is embryonic lethal. In contrast to mammals, cardiovascular function is not essential for early zebrafish development because the embryos obtain adequate oxygen by diffusion. In this study, we use targeted protein depletion coupled with protein-based rescue experiments to investigate the involvement of perlecan and its C-terminal domain V/endorepellin in zebrafish development. The perlecan morphants show a severe myopathy characterized by abnormal actin filament orientation and disorganized sarcomeres, suggesting an involvement of perlecan in myopathies. In the perlecan morphants, primary intersegmental vessel sprouts, which develop through angiogenesis, fail to extend and show reduced protrusive activity. Live videomicroscopy confirms the abnormal swimming pattern caused by the myopathy and anomalous head and trunk vessel circulation. The phenotype is partially rescued by microinjection of human perlecan or endorepellin. These findings indicate that perlecan is essential for the integrity of somitic muscle and developmental angiogenesis and that endorepellin mediates most of these biological activities.

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Nakamura, Kuniyuki, Tomoko Ikeuchi, Kazuki Nara, Craig S. Rhodes, Peipei Zhang, Yuta Chiba, Saiko Kazuno, et al. "Perlecan regulates pericyte dynamics in the maintenance and repair of the blood–brain barrier." Journal of Cell Biology 218, no. 10 (September 20, 2019): 3506–25. http://dx.doi.org/10.1083/jcb.201807178.

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Ischemic stroke causes blood–brain barrier (BBB) breakdown due to significant damage to the integrity of BBB components. Recent studies have highlighted the importance of pericytes in the repair process of BBB functions triggered by PDGFRβ up-regulation. Here, we show that perlecan, a major heparan sulfate proteoglycan of basement membranes, aids in BBB maintenance and repair through pericyte interactions. Using a transient middle cerebral artery occlusion model, we found larger infarct volumes and more BBB leakage in conditional perlecan (Hspg2)-deficient (Hspg2−/−-TG) mice than in control mice. Control mice showed increased numbers of pericytes in the ischemic lesion, whereas Hspg2−/−-TG mice did not. At the mechanistic level, pericytes attached to recombinant perlecan C-terminal domain V (perlecan DV, endorepellin). Perlecan DV enhanced the PDGF-BB–induced phosphorylation of PDGFRβ, SHP-2, and FAK partially through integrin α5β1 and promoted pericyte migration. Perlecan therefore appears to regulate pericyte recruitment through the cooperative functioning of PDGFRβ and integrin α5β1 to support BBB maintenance and repair following ischemic stroke.

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Miosge, Nicolai, Timo Simniok, Patricia Sprysch, and Rainer Herken. "The Collagen Type XVIII Endostatin Domain Is Co-localized with Perlecan in Basement Membranes in Vivo." Journal of Histochemistry & Cytochemistry 51, no. 3 (March 2003): 285–96. http://dx.doi.org/10.1177/002215540305100303.

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The C-terminal globular endostatin domain of collagen type XVIII is anti-angiogenic in a variety of experimental tumor models, and clinical trials to test it as an anti-tumor agent are already under way. In contrast, many of its cell biological properties are still unknown. We systematically localized the mRNA of collagen type XVIII with the help of in situ hybridization (ISH) and detected it in epithelial and mesenchymal cells of almost all organ systems throughout mouse development. Light and electron microscopic immunohistochemistry (IHC) revealed that the endostatin domain is a widespread component of almost all epithelial basement membranes in all major developing organs, and in all basement membranes of capillaries and blood vessels. Furthermore, quantitative immunogold double labeling demonstrated a co-localization of 50% of the detected endostatin domain together with perlecan in basement membranes in vivo. We conclude that the endostatin domain of collagen type XVIII plays a role, even in early stages of mouse development, other than regulating angiogenesis. In the adult, the endostatin domain could well be involved in connecting collagen type XVIII to the basement membrane scaffolds. At least in part, perlecan appears to be an adaptor molecule for the endostatin domain in basement membranes in vivo.

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Mullen, Gregory P., Teresa M. Rogalski, Jason A. Bush, Poupak Rahmani Gorji, and Donald G. Moerman. "Complex Patterns of Alternative Splicing Mediate the Spatial and Temporal Distribution of Perlecan/UNC-52 in Caenorhabditis elegans." Molecular Biology of the Cell 10, no. 10 (October 1999): 3205–21. http://dx.doi.org/10.1091/mbc.10.10.3205.

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The unc-52 gene encodes the nematode homologue of mammalian perlecan, the major heparan sulfate proteoglycan of the extracellular matrix. This is a large complex protein with regions similar to low-density lipoprotein receptors, laminin, and neural cell adhesion molecules (NCAMs). In this study, we extend our earlier work and demonstrate that a number of complex isoforms of this protein are expressed through alternative splicing. We identified three major classes of perlecan isoforms: a short form lacking the NCAM region and the C-terminal agrin-like region; a medium form containing the NCAM region, but still lacking the agrin-like region; and a newly identified long form that contains all five domains present in mammalian perlecan. Using region-specific antibodies andunc-52 mutants, we reveal a complex spatial and temporal expression pattern for these UNC-52 isoforms. As well, using a series of mutations affecting different regions and thus different isoforms of UNC-52, we demonstrate that the medium NCAM-containing isoforms are sufficient for myofilament lattice assembly in developing nematode body-wall muscle. Neither short isoforms nor isoforms containing the C-terminal agrin-like region are essential for sarcomere assembly or muscle cell attachment, and their role in development remains unclear.

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Chung, C. Y., and H. P. Erickson. "Glycosaminoglycans modulate fibronectin matrix assembly and are essential for matrix incorporation of tenascin-C." Journal of Cell Science 110, no. 12 (June 15, 1997): 1413–19. http://dx.doi.org/10.1242/jcs.110.12.1413.

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We have investigated the role of glycosaminoglycans in fibronectin matrix assembly and the incorporation of tenascin-C into matrix fibrils. Chinese hamster ovary cell mutants with a total block in heparan and chondroitin sulfate production failed to assemble a fibronectin matrix, and incorporated no tenascin-C. Another mutant with reduced heparan sulfate produced a normal fibronectin matrix but failed to incorporate tenascin-C. Excess soluble glycosaminoglycans inhibited the binding of tenascin-C to purified fibronectin in ELISA, and completely blocked incorporation into matrix fibrils. Treating cultured cells with xyloside, which interferes with glycosaminoglycan attachment to proteoglycans, also completely blocked their ability to incorporate tenascin-C into matrix fibrils. We conclude that proteoglycans bound to fibronectin fibrils play a major role in binding tenascin-C to these fibrils. We examined more closely the large heparan sulfate proteoglycan, perlecan, and found that it co-localizes with tenascin-C and fibronectin in the matrix. The perlecan binding site in tenascin-C was mapped to the fibronectin type III domains 3–5, but this binding was strongly enhanced for the small splice variant, which is the major form incorporated into the matrix. Apparently when the alternative splice segment is inserted after domain 5 it inhibits perlecan binding. Thus heparan sulfate glycosaminoglycans, and perlecan in particular, may play a role in incorporation of the small splice variant of tenascin-C into fibronectin matrix fibrils.

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Bix, Gregory, Jian Fu, Eva M. Gonzalez, Laura Macro, Amy Barker, Shelly Campbell, Mary M. Zutter, et al. "Endorepellin causes endothelial cell disassembly of actin cytoskeleton and focal adhesions through α2β1 integrin." Journal of Cell Biology 166, no. 1 (July 5, 2004): 97–109. http://dx.doi.org/10.1083/jcb.200401150.

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Endorepellin, the COOH-terminal domain of the heparan sulfate proteoglycan perlecan, inhibits several aspects of angiogenesis. We provide evidence for a novel biological axis that links a soluble fragment of perlecan protein core to the major cell surface receptor for collagen I, α2β1 integrin, and provide an initial investigation of the intracellular signaling events that lead to endorepellin antiangiogenic activity. The interaction between endorepellin and α2β1 integrin triggers a unique signaling pathway that causes an increase in the second messenger cAMP; activation of two proximal kinases, protein kinase A and focal adhesion kinase; transient activation of p38 mitogen-activated protein kinase and heat shock protein 27, followed by a rapid down-regulation of the latter two proteins; and ultimately disassembly of actin stress fibers and focal adhesions. The end result is a profound block of endothelial cell migration and angiogenesis. Because perlecan is present in both endothelial and smooth muscle cell basement membranes, proteolytic activity during the initial stages of angiogenesis could liberate antiangiogenic fragments from blood vessels' walls, including endorepellin.

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Hayashi, K., J. A. Madri, and P. D. Yurchenco. "Endothelial cells interact with the core protein of basement membrane perlecan through beta 1 and beta 3 integrins: an adhesion modulated by glycosaminoglycan." Journal of Cell Biology 119, no. 4 (November 15, 1992): 945–59. http://dx.doi.org/10.1083/jcb.119.4.945.

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Aortic endothelial cells adhere to the core protein of murine perlecan, a heparan sulfate proteoglycan present in endothelial basement membrane. We found that cell adhesion was partially inhibited by beta 1 integrin-specific mAb and almost completely blocked by a mixture of beta 1 and alpha v beta 3 antibodies. Furthermore, adhesion was partially inhibited by a synthetic peptide containing the perlecan domain III sequence LPASFRGDKVTSY (c-RGD) as well as by GRGDSP, but not by GRGESP. Both antibodies contributed to the inhibition of cell adhesion to immobilized c-RGD whereas only beta 1-specific antibody blocked residual cell adhesion to proteoglycan core in the presence of maximally inhibiting concentrations of soluble RGD peptide. A fraction of endothelial surface-labeled detergent lysate bound to a core affinity column and 147-, 116-, and 85-kD proteins were eluted with NaCl and EDTA. Polyclonal anti-beta 1 and anti-beta 3 integrin antibodies immunoprecipitated 116/147 and 85/147 kD surface-labeled complexes, respectively. Cell adhesion to perlecan was low compared to perlecan core, and cell adhesion to core, but not to immobilized c-RGD, was selectively inhibited by soluble heparin and heparan sulfates. This inhibition by heparin was also observed with laminin and fibronectin and, in the case of perlecan, was found to be independent of heparin binding to substrate. These data support the hypothesis that endothelial cells interact with the core protein of perlecan through beta 1 and beta 3 integrins, that this binding is partially RGD-independent, and that this interaction is selectively sensitive to a cell-mediated effect of heparin/heparan sulfates which may act as regulatory ligands.

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French, Margaret M., Ronald R. Gomes, Rupert Timpl, Magnus Höök, Kirk Czymmek, Mary C. Farach-Carson, and Daniel D. Carson. "Chondrogenic Activity of the Heparan Sulfate Proteoglycan Perlecan Maps to the N-terminal Domain I." Journal of Bone and Mineral Research 17, no. 1 (January 1, 2002): 48–55. http://dx.doi.org/10.1359/jbmr.2002.17.1.48.

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9

Nyström, Alexander, Zabeena P. Shaik, Donald Gullberg, Thomas Krieg, Beate Eckes, Roy Zent, Ambra Pozzi, and Renato V. Iozzo. "Role of tyrosine phosphatase SHP-1 in the mechanism of endorepellin angiostatic activity." Blood 114, no. 23 (November 26, 2009): 4897–906. http://dx.doi.org/10.1182/blood-2009-02-207134.

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Abstract Endorepellin, the C-terminal domain of perlecan, is a powerful angiogenesis inhibitor. To dissect the mechanism of endorepellin-mediated endothelial silencing, we used an antibody array against multiple tyrosine kinase receptors. Endorepellin caused a widespread reduction in phosphorylation of key receptors involved in angiogenesis and a concurrent increase in phosphatase activity in endothelial cells and tumor xenografts. These effects were efficiently hampered by function-blocking antibodies against integrin α2β1, the functional endorepellin receptor. The Src homology-2 protein phosphatase-1 (SHP-1) coprecipitated with integrin α2 and was phosphorylated in a dynamic fashion after endorepellin stimulation. Genetic evidence was provided by lack of an endorepellin-evoked phosphatase response in microvascular endothelial cells derived from integrin α2β1−/− mice and by response to endorepellin in cells genetically engineered to express the α2β1 integrin, but not in cells either lacking this receptor or expressing a chimera harboring the integrin α2 ectodomain fused to the α1 intracellular domain. siRNA-mediated knockdown of integrin α2 caused a dose-dependent reduction of SHP-1. Finally, the levels of SHP-1 and its enzymatic activity were substantially reduced in multiple organs from α2β1−/− mice. Our results show that SHP-1 is an essential mediator of endorepellin activity and discover a novel functional interaction between the integrin α2 subunit and SHP-1.

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GARBE, Jörg H. O., Walter GÖHRING, Karlheinz MANN, Rupert TIMPL, and Takako SASAKI. "Complete sequence, recombinant analysis and binding to laminins and sulphated ligands of the N-terminal domains of laminin α3B and α5 chains." Biochemical Journal 362, no. 2 (February 22, 2002): 213–21. http://dx.doi.org/10.1042/bj3620213.

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The N-terminal sequences of mouse laminin α3B and α5 chains have been completed and demonstrate the presence of a signal peptide followed by a complete laminin N-terminal (LN) module (domain VI). These signal peptides were released after recombinant production of larger fragments comprising domains VI/V (45–65kDa) from this region yielding properly folded proteins, which were secreted from HEK-293—EBNA cells. Pepsin digestion of these fragments yielded products of 25–35kDa, which consisted only of domain V. The αVI/V fragments were able to inhibit self-assembly of laminin-1, with those from the α3B and α5 chains being more active than those from α1 and α2 chains. Domain V fragments, however, showed a reduced activity, indicating the major contribution of the LN module in inhibition. These interactions were confirmed by surface-plasmon-resonance assays demonstrating moderate affinities (Kd = 0.02 to > 6μM) for the binding to laminin-1. This indicated that laminins containing α3B or α5 chains should also be able to form non-covalent networks by polymerization. The LN modules also showed heparin binding in affinity chromatography, which was strongest for α1/α2, moderate for α3B, whereas no binding was observed for α5. They all bound to heparan sulphate chains of perlecan and to sulphatides, with a lower variability in binding activity. Specific antibodies were raised against α3BVI/V and α5VI/V and were shown to stain basement membrane zones in various mouse tissues. These antibodies also allowed the identification of a new laminin assembly form 5B consisting of α3B, β3 and γ2 chains.

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Brown, Judith C., Takako Sasaki, Walter Gohring, Yoshihiko Yamada, and Rupert Timpl. "The C-Terminal Domain V of Perlecan Promotes beta1 Integrin-Mediated Cell Adhesion, Binds Heparin, Nidogen and Fibulin-2 and Can be Modified by Glycosaminoglycans." European Journal of Biochemistry 250, no. 1 (November 15, 1997): 39–46. http://dx.doi.org/10.1111/j.1432-1033.1997.t01-1-00039.x.

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12

Ettner, Norbert, Walter Göhring, Takako Sasaki, Karlheinz Mann, and Rupert Timpl. "The N-terminal globular domain of the laminin α1 chain binds to α1β1 and α2β1 integrins and to the heparan sulfate-containing domains of perlecan." FEBS Letters 430, no. 3 (July 3, 1998): 217–21. http://dx.doi.org/10.1016/s0014-5793(98)00601-2.

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13

Wu, Rong-Rong, and John R. Couchman. "cDNA Cloning of the Basement Membrane Chondroitin Sulfate Proteoglycan Core Protein, Bamacan: A Five Domain Structure Including Coiled-Coil Motifs." Journal of Cell Biology 136, no. 2 (January 27, 1997): 433–44. http://dx.doi.org/10.1083/jcb.136.2.433.

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Basement membranes contain several proteoglycans, and those bearing heparan sulfate glycosaminoglycans such as perlecan and agrin usually predominate. Most mammalian basement membranes also contain chondroitin sulfate, and a core protein, bamacan, has been partially characterized. We have now obtained cDNA clones encoding the entire bamacan core protein of Mr = 138 kD, which reveal a five domain, head-rod-tail configuration. The head and tail are potentially globular, while the central large rod probably forms coiled-coil structures, with one large central and several very short interruptions. This molecular architecture is novel for an extracellular matrix molecule, but it resembles that of a group of intracellular proteins, including some proposed to stabilize the mitotic chromosome scaffold. We have previously proposed a similar stabilizing role for bamacan in the basement membrane matrix. The protein sequence has low overall homology, apart from very small NH2- and COOH-terminal motifs. At the junctions between the distal globular domains and the coiled-coil regions lie glycosylation sites, with up to three N-linked oligosaccharides and probably three chondroitin chains. Three other Ser-Gly dipeptides are unfavorable for substitution. Fusion protein antibodies stained basement membranes in a pattern commensurate with bamacan, and they also Western blotted bamacan core protein from rat L2 cell cultures. The antibodies could also specifically immunoprecipitate an in vitro transcription/translation product from a full-length bamacan cDNA. The unusual structure of this proteoglycan is indicative of specific functional roles in basement membrane physiology, commensurate with its distinct expression in development and changes in disease models.

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Aviezer, D., R. V. Iozzo, D. M. Noonan, and A. Yayon. "Suppression of autocrine and paracrine functions of basic fibroblast growth factor by stable expression of perlecan antisense cDNA." Molecular and Cellular Biology 17, no. 4 (April 1997): 1938–46. http://dx.doi.org/10.1128/mcb.17.4.1938.

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Heparan sulfate proteoglycans (HSPG) play a critical role in the formation of distinct fibroblast growth factor (FGF)-HS complexes, augmenting high-affinity binding and receptor activation. Perlecan, a secreted HSPG abundant in proliferating cells, is capable of inducing FGF-receptor interactions in vitro and angiogenesis in vivo. Stable and specific reduction of perlecan levels in mouse NIH 3T3 fibroblasts and human metastatic melanoma cells has been achieved by expression of antisense cDNA corresponding to the N-terminal and HS attachment domains of perlecan. Long-term perlecan downregulation is evidenced by reduced levels of perlecan mRNA and core protein as indicated by Northern blot analysis, immunoblots, and immunohistochemistry, using DNA probes and antibodies specific to mouse or human perlecan. The response of antisense perlecan-expressing cells to increasing concentrations of basic FGF (bFGF) is dramatically reduced in comparison to that in wild-type or vector-transfected cells, as measured by thymidine incorporation and rate of proliferation. Furthermore, receptor binding and affinity labeling of antisense perlecan-transfected cells with 125I-bFGF is markedly inhibited, indicating that eliminating perlecan expression results in reduced high-affinity bFGF binding. Both the binding and mitogenic response of antisense-perlecan-expressing clones to bFGF can be rescued by exogenous heparin or perlecan. These results support the notion that perlecan is a major accessory receptor for bFGF in mouse fibroblasts and human melanomas and point to the possible use of perlecan antisense constructs as specific modulators of bFGF-mediated responses.

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Sun, Zheying, Scott S. Kemp, Prisca K. Lin, Kalia N. Aguera, and George E. Davis. "Endothelial k-RasV12 Expression Induces Capillary Deficiency Attributable to Marked Tube Network Expansion Coupled to Reduced Pericytes and Basement Membranes." Arteriosclerosis, Thrombosis, and Vascular Biology 42, no. 2 (February 2022): 205–22. http://dx.doi.org/10.1161/atvbaha.121.316798.

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Objective: We sought to determine how endothelial cell (EC) expression of the activating k-Ras (kirsten rat sarcoma 2 viral oncogene homolog) mutation, k-RasV12, affects their ability to form lumens and tubes and interact with pericytes during capillary assembly Approach and Results: Using defined bioassays where human ECs undergo observable tubulogenesis, sprouting behavior, pericyte recruitment to EC-lined tubes, and pericyte-induced EC basement membrane deposition, we assessed the impact of EC k-RasV12 expression on these critical processes that are necessary for proper capillary network formation. This mutation, which is frequently seen in human ECs within brain arteriovenous malformations, was found to markedly accentuate EC lumen formation mechanisms, with strongly accelerated intracellular vacuole formation, vacuole fusion, and lumen expansion and with reduced sprouting behavior, leading to excessively widened tube networks compared with control ECs. These abnormal tubes demonstrate strong reductions in pericyte recruitment and pericyte-induced EC basement membranes compared with controls, with deficiencies in fibronectin, collagen type IV, and perlecan deposition. Analyses of signaling during tube formation from these k-RasV12 ECs reveals strong enhancement of Src (Src proto-oncogene, non-receptor tyrosine kinase), Pak2 (P21 [RAC1 (Rac family small GTPase 1)] activated kinase 2), b-Raf (v-raf murine sarcoma viral oncogene homolog B1), Erk (extracellular signal–related kinase), and Akt (AK strain transforming) activation and increased expression of PKCε (protein kinase C epsilon), MT1-MMP (membrane-type 1 matrix metalloproteinase), acetylated tubulin and CDCP1 (CUB domain-containing protein 1; most are known EC lumen regulators). Pharmacological blockade of MT1-MMP, Src, Pak, Raf, Mek (mitogen-activated protein kinase) kinases, Cdc42 (cell division cycle 42)/Rac1, and Notch markedly interferes with lumen and tube formation from these ECs. Conclusions: Overall, this novel work demonstrates that EC expression of k-RasV12 disrupts capillary assembly due to markedly excessive lumen formation coupled with strongly reduced pericyte recruitment and basement membrane deposition, which are critical pathogenic features predisposing the vasculature to develop arteriovenous malformations.

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Ayvazian, Laurence, Brigitte Kerfelec, Simone Granon, Edith Foglizzo, Isabelle Crenon, Christophe Dubois, and Catherine Chapus. "The Lipase C-terminal Domain." Journal of Biological Chemistry 276, no. 17 (January 11, 2001): 14014–18. http://dx.doi.org/10.1074/jbc.m010328200.

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17

David, Charles J., and James L. Manley. "The RNA polymerase C-terminal domain." Transcription 2, no. 5 (September 2011): 221–25. http://dx.doi.org/10.4161/trns.2.5.17272.

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18

Gonzalez, Eva M., Charles C. Reed, Gregory Bix, Jian Fu, Yue Zhang, Bagavathi Gopalakrishnan, Daniel S. Greenspan, and Renato V. Iozzo. "BMP-1/Tolloid-like Metalloproteases Process Endorepellin, the Angiostatic C-terminal Fragment of Perlecan." Journal of Biological Chemistry 280, no. 8 (December 9, 2004): 7080–87. http://dx.doi.org/10.1074/jbc.m409841200.

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Clifton, Matthew C., Robert N. Kirchdoerfer, Kateri Atkins, Jan Abendroth, Amy Raymond, Rena Grice, Steve Barnes, et al. "Structure of theReston ebolavirusVP30 C-terminal domain." Acta Crystallographica Section F Structural Biology Communications 70, no. 4 (March 25, 2014): 457–60. http://dx.doi.org/10.1107/s2053230x14003811.

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The ebolaviruses can cause severe hemorrhagic fever. Essential to the ebolavirus life cycle is the protein VP30, which serves as a transcriptional cofactor. Here, the crystal structure of the C-terminal, NP-binding domain of VP30 fromReston ebolavirusis presented. Reston VP30 and Ebola VP30 both form homodimers, but the dimeric interfaces are rotated relative to each other, suggesting subtle inherent differences or flexibility in the dimeric interface.

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Broekelmann, Thomas J., Christopher H. Ciliberto, Adrian Shifren, and Robert P. Mecham. "C-terminal domain modification in mature elastin." Matrix Biology 27 (December 2008): 40. http://dx.doi.org/10.1016/j.matbio.2008.09.342.

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Botella, L. M., and Antonio Nieto. "The C-terminal DNA-binding domain of." MGG Molecular & General Genetics 251, no. 4 (1996): 422. http://dx.doi.org/10.1007/s004380050185.

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Bull, P., K. L. Morley, M. F. Hoekstra, T. Hunter, and I. M. Verma. "The mouse c-rel protein has an N-terminal regulatory domain and a C-terminal transcriptional transactivation domain." Molecular and Cellular Biology 10, no. 10 (October 1990): 5473–85. http://dx.doi.org/10.1128/mcb.10.10.5473-5485.1990.

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We have shown that the murine c-rel protein can act as a transcriptional transactivator in both yeast and mammalian cells. Fusion proteins generated by linking rel sequences to the DNA-binding domain of the yeast transcriptional activator GAL4 activate transcription from a reporter gene linked in cis to a GAL4 binding site. The full-length mouse c-rel protein (588 amino acids long) is a poor transactivator; however, the C-terminal portion of the protein between amino acid residues 403 to 568 is a potent transcriptional transactivator. Deletion of the N-terminal half of the c-rel protein augments its transactivation function. We propose that c-rel protein has an N-terminal regulatory domain and a C-terminal transactivation domain which together modulate its function as a transcriptional transactivator.

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Bull, P., K. L. Morley, M. F. Hoekstra, T. Hunter, and I. M. Verma. "The mouse c-rel protein has an N-terminal regulatory domain and a C-terminal transcriptional transactivation domain." Molecular and Cellular Biology 10, no. 10 (October 1990): 5473–85. http://dx.doi.org/10.1128/mcb.10.10.5473.

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We have shown that the murine c-rel protein can act as a transcriptional transactivator in both yeast and mammalian cells. Fusion proteins generated by linking rel sequences to the DNA-binding domain of the yeast transcriptional activator GAL4 activate transcription from a reporter gene linked in cis to a GAL4 binding site. The full-length mouse c-rel protein (588 amino acids long) is a poor transactivator; however, the C-terminal portion of the protein between amino acid residues 403 to 568 is a potent transcriptional transactivator. Deletion of the N-terminal half of the c-rel protein augments its transactivation function. We propose that c-rel protein has an N-terminal regulatory domain and a C-terminal transactivation domain which together modulate its function as a transcriptional transactivator.

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Jones, Janice C., Hemali P. Phatnani, Timothy A. Haystead, Justin A. MacDonald, S. Munir Alam, and Arno L. Greenleaf. "C-terminal Repeat Domain Kinase I Phosphorylates Ser2 and Ser5 of RNA Polymerase II C-terminal Domain Repeats." Journal of Biological Chemistry 279, no. 24 (March 26, 2004): 24957–64. http://dx.doi.org/10.1074/jbc.m402218200.

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Koiwa, H., S. Hausmann, W. Y. Bang, A. Ueda, N. Kondo, A. Hiraguri, T. Fukuhara, et al. "Arabidopsis C-terminal domain phosphatase-like 1 and 2 are essential Ser-5-specific C-terminal domain phosphatases." Proceedings of the National Academy of Sciences 101, no. 40 (September 23, 2004): 14539–44. http://dx.doi.org/10.1073/pnas.0403174101.

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DeBell, Karen, Laurie Graham, Ilona Reischl, Carmen Serrano, Ezio Bonvini, and Barbara Rellahan. "Intramolecular Regulation of Phospholipase C-γ1 by Its C-Terminal Src Homology 2 Domain." Molecular and Cellular Biology 27, no. 3 (November 20, 2006): 854–63. http://dx.doi.org/10.1128/mcb.01400-06.

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ABSTRACT Phosphoinositide-specific phospholipase C-γ1 (PLC-γ1) is a key enzyme that governs cellular functions such as gene transcription, secretion, proliferation, motility, and development. Here, we show that PLC-γ1 is regulated via a novel autoinhibitory mechanism involving its carboxy-terminal Src homology (SH2C) domain. Mutation of the SH2C domain tyrosine binding site led to constitutive PLC-γ1 activation. The amino-terminal split pleckstrin homology (sPHN) domain was found to regulate the accessibility of the SH2C domain. PLC-γ1 constructs with mutations in tyrosine 509 and phenylalanine 510 in the sPHN domain no longer required an intact amino-terminal Src homology (SH2N) domain or phosphorylation of tyrosine 775 or 783 for activation. These data are consistent with a model in which the SH2C domain is blocked by an intramolecular interaction(s) that is released upon cellular activation by occupancy of the SH2N domain.

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Kosoy, Ana, and Matthew J. O'Connell. "Regulation of Chk1 by Its C-terminal Domain." Molecular Biology of the Cell 19, no. 11 (November 2008): 4546–53. http://dx.doi.org/10.1091/mbc.e08-04-0444.

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Chk1 is a protein kinase that is the effector molecule in the G2 DNA damage checkpoint. Chk1 homologues have an N-terminal kinase domain, and a C-terminal domain of ∼200 amino acids that contains activating phosphorylation sites for the ATM/R kinases, though the mechanism of activation remains unknown. Structural studies of the human Chk1 kinase domain show an open conformation; the activity of the kinase domain alone is substantially higher in vitro than full-length Chk1, and coimmunoprecipitation studies suggest the C-terminal domain may contain an autoinhibitory activity. However, we show that truncation of the C-terminal domain inactivates Chk1 in vivo. We identify additional mutations within the C-terminal domain that activate ectopically expressed Chk1 without the need for activating phosphorylation. When expressed from the endogenous locus, activated alleles show a temperature-sensitive loss of function, suggesting these mutations confer a semiactive state to the protein. Intragenic suppressors of these activated alleles cluster to regions in the catalytic domain on the face of the protein that interacts with substrate, suggesting these are the regions that interact with the C-terminal domain. Thus, rather than being an autoinhibitory domain, the C-terminus of Chk1 also contains domains critical for adopting an active configuration.

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Ivanov, D., O. V. Tsodikov, J. Kasanov, T. Ellenberger, G. Wagner, and T. Collins. "Domain-swapped dimerization of the HIV-1 capsid C-terminal domain." Proceedings of the National Academy of Sciences 104, no. 11 (March 5, 2007): 4353–58. http://dx.doi.org/10.1073/pnas.0609477104.

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PERRY, Ashlee, Lu-Yun LIAN, and Nigel S. SCRUTTON. "Two-iron rubredoxin of Pseudomonas oleovorans: production, stability and characterization of the individual iron-binding domains by optical, CD and NMR spectroscopies." Biochemical Journal 354, no. 1 (February 8, 2001): 89–98. http://dx.doi.org/10.1042/bj3540089.

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A minigene encoding the C-terminal domain of the 2Fe rubredoxin of Pseudomonas oleovorans was created from the parental alk G gene contained in the expression plasmid pKK223-3. The vector directed the high-level production of the C-terminal domain of this rubredoxin; a simple procedure was used to purify the recombinant domain in the 1Fe form. The 1Fe form of the C-terminal domain was readily converted into the apoprotein and cadmium forms after precipitation with trichloroacetic acid and resolubilization in the presence or absence of cadmium chloride respectively. In steady-state assays, the recombinant 1Fe C-terminal domain is redox-active and able to transfer electrons from reduced rubredoxin reductase to cytochrome c. The absorption spectrum and dichroic features of the CD spectrum for the iron- and cadmium-substituted C-terminal domain are similar to those reported for the iron- and cadmium-substituted Desulfovibrio gigas rubredoxin [Henehen, Pountney, Zerbe and Vasak (1993) Protein Sci. 2, 1756–1764]. Difference absorption spectroscopy of the cadmium-substituted C-terminal domain revealed the presence of four Gaussian-resolved maxima at 202, 225, 240 and 276nm; from J⊘rgensen's electronegativity theory, the 240nm band is attributable to a CysS-Cd(II) charge-transfer excitation. Attempts to express the N-terminal domain of the 2Fe rubredoxin directly from a minigene were unsuccessful. However, the N-terminal domain was isolated through cleavage of an engineered 2Fe rubredoxin in which a factor Xa proteolysis site had been introduced into the putative interdomain linker. The N-terminal domain is characterized by absorption spectra typical of the 1Fe rubredoxins. The domain is folded as determined by CD and NMR spectroscopies and is redox-active. However, the N-terminal domain is less stable than the isolated C-terminal domain, a finding consistent with the known properties of the full-length 2Fe and cadmium-substituted Ps. oleovorans rubredoxin.

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Shinoda, K., K. Yura, and M. Go. "Dynamical properties of prion protein C-terminal domain." Seibutsu Butsuri 39, supplement (1999): S130. http://dx.doi.org/10.2142/biophys.39.s130_4.

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Rallabandi, Harikrishna Reddy, Palanivel Ganesan, and Young Jun Kim. "Targeting the C-Terminal Domain Small Phosphatase 1." Life 10, no. 5 (May 8, 2020): 57. http://dx.doi.org/10.3390/life10050057.

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The human C-terminal domain small phosphatase 1 (CTDSP1/SCP1) is a protein phosphatase with a conserved catalytic site of DXDXT/V. CTDSP1’s major activity has been identified as dephosphorylation of the 5th Ser residue of the tandem heptad repeat of the RNA polymerase II C-terminal domain (RNAP II CTD). It is also implicated in various pivotal biological activities, such as acting as a driving factor in repressor element 1 (RE-1)-silencing transcription factor (REST) complex, which silences the neuronal genes in non-neuronal cells, G1/S phase transition, and osteoblast differentiation. Recent findings have denoted that negative regulation of CTDSP1 results in suppression of cancer invasion in neuroglioma cells. Several researchers have focused on the development of regulating materials of CTDSP1, due to the significant roles it has in various biological activities. In this review, we focused on this emerging target and explored the biological significance, challenges, and opportunities in targeting CTDSP1 from a drug designing perspective.

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Hsieh, Tung-Ju, Lynn Farh, Wai Mun Huang, and Nei-Li Chan. "Structure of the Topoisomerase IV C-terminal Domain." Journal of Biological Chemistry 279, no. 53 (October 4, 2004): 55587–93. http://dx.doi.org/10.1074/jbc.m408934200.

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Huyton, Trevor, Paul A. Bates, Xiaodong Zhang, Michael J. E. Sternberg, and Paul S. Freemont. "The BRCA1 C-terminal domain: structure and function." Mutation Research/DNA Repair 460, no. 3-4 (August 2000): 319–32. http://dx.doi.org/10.1016/s0921-8777(00)00034-3.

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Krstenansky, John L., Thomas J. Owen, Mark T. Yates, and Simon J. T. Mao. "The C-terminal binding domain of hirullin P18." FEBS Letters 269, no. 2 (September 3, 1990): 425–29. http://dx.doi.org/10.1016/0014-5793(90)81208-6.

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Martinac, Adam D., Navid Bavi, Marien D. Cortes, Omid Bavi, Takeshi Nomura, Boris Martinac, and Eduardo Perozo. "Structural Dynamics of the MSCL C-Terminal Domain." Biophysical Journal 112, no. 3 (February 2017): 413a. http://dx.doi.org/10.1016/j.bpj.2016.11.2569.

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Higuchi, Itsuro, Hidetoshi Fukunaga, Fusako Usuki, Takashi Moritoyo, and Mitsuhiro Osame. "Phenotypic Duchenne muscular dystrophy with C-terminal domain." Pediatric Neurology 8, no. 4 (July 1992): 310–12. http://dx.doi.org/10.1016/0887-8994(92)90373-7.

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Burgute, Bhagyashri D., Vivek S. Peche, Rolf Müller, Jan Matthias, Berthold Gaßen, Ludwig Eichinger, Gernot Glöckner, and Angelika A. Noegel. "The C-Terminal SynMuv/DdDUF926 Domain Regulates the Function of the N-Terminal Domain of DdNKAP." PLOS ONE 11, no. 12 (December 20, 2016): e0168617. http://dx.doi.org/10.1371/journal.pone.0168617.

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Sanford, J. C., Y. Pan, and M. Wessling-Resnick. "Properties of Rab5 N-terminal domain dictate prenylation of C-terminal cysteines." Molecular Biology of the Cell 6, no. 1 (January 1995): 71–85. http://dx.doi.org/10.1091/mbc.6.1.71.

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Rab5 is a Ras-related GTP-binding protein that is post-translationally modified by prenylation. We report here that an N-terminal domain contained within the first 22 amino acids of Rab5 is critical for efficient geranylgeranylation of the protein's C-terminal cysteines. This domain is immediately upstream from the "phosphate binding loop" common to all GTP-binding proteins and contains a highly conserved sequence recognized among members of the Rab family, referred to here as the YXYLFK motif. A truncation mutant that lacks this domain (Rab5(23-215) fails to become prenylated. However, a chimeric peptide with the conserved motif replacing cognate Rab5 sequence (MAYDYLFKRab5(23-215) does become post-translationally modified, demonstrating that the presence of this simple six amino acid N-terminal element enables prenylation at Rab5's C-terminus. H-Ras/Rab5 chimeras that include the conserved YXYLFK motif at the N-terminus do not become prenylated, indicating that, while this element may be necessary for prenylation of Rab proteins, it alone is not sufficient to confer properties to a heterologous protein to enable substrate recognition by the Rab geranylgeranyl transferase. Deletion analysis and studies of point mutants further reveal that the lysine residue of the YXYLFK motif is an absolute requirement to enable geranylgeranylation of Rab proteins. Functional studies support the idea that this domain is not required for guanine nucleotide binding since prenylation-defective mutants still bind GDP and are protected from protease digestion in the presence of GTP gamma S. We conclude that the mechanism of Rab geranylgeranylation involves key elements of the protein's tertiary structure including a conserved N-terminal amino acid motif (YXYLFK) that incorporates a critical lysine residue.

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Moriyama, Kenji, and Ichiro Yahara. "Human CAP1 is a key factor in the recycling of cofilin and actin for rapid actin turnover." Journal of Cell Science 115, no. 8 (April 15, 2002): 1591–601. http://dx.doi.org/10.1242/jcs.115.8.1591.

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Cofilin-ADF (actin-depolymerizing factor) is an essential driver of actin-based motility. We discovered two proteins, p65 and p55, that are components of the actin-cofilin complex in a human HEK293 cell extract and identified p55 as CAP1/ASP56, a human homologue of yeast CAP/SRV2(cyclase-associated protein). CAP is a bifunctional protein with an N-terminal domain that binds to Ras-responsive adenylyl cyclase and a C-terminal domain that inhibits actin polymerization. Surprisingly, we found that the N-terminal domain of CAP1, but not the C-terminal domain, is responsible for the interaction with the actin-cofilin complex. The N-terminal domain of CAP1 was also found to accelerate the depolymerization of F-actin at the pointed end,which was further enhanced in the presence of cofilin and/or the C-terminal domain of CAP1. Moreover, CAP1 and its C-terminal domain were observed to facilitate filament elongation at the barbed end and to stimulate ADP-ATP exchange on G-actin, a process that regenerates easily polymerizable G-actin. Although cofilin inhibited the nucleotide exchange on G-actin even in the presence of the C-terminal domain of CAP1, its N-terminal domain relieved this inhibition. Thus, CAP1 plays a key role in speeding up the turnover of actin filaments by effectively recycling cofilin and actin and through its effect on both ends of actin filament.

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Cornell, R. B., G. B. Kalmar, R. J. Kay, M. A. Johnson, J. S. Sanghera, and S. L. Pelech. "Functions of the C-terminal domain of CTP: phosphocholine cytidylyltransferase. Effects of C-terminal deletions on enzyme activity, intracellular localization and phosphorylation potential." Biochemical Journal 310, no. 2 (September 1, 1995): 699–708. http://dx.doi.org/10.1042/bj3100699.

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The role of the C-terminal domain of CTP: phosphocholine cytidylyltransferase (CT) was explored by the creation of a series of deletion mutations in rat liver cDNA, which were expressed in COS cells as a major protein component. Deletion of up to 55 amino acids from the C-terminus had no effect on the activity of the enzyme, its stimulation by lipid vesicles or on its intracellular distribution between soluble and membrane-bound forms. However, deletion of the C-terminal 139 amino acids resulted in a 90% decrease in activity, loss of response to lipid vesicles and a significant decrease in the fraction of membrane-bound enzyme. Identification of the domain that is phosphorylated in vivo was determined by analysis of 32P-labelled CT mutants and by chymotrypsin proteolysis of purified CT that was 32P-labelled in vivo. Phosphorylation was restricted to the C-terminal 52 amino acids (domain P) and occurred on multiple sites. CT phosphorylation in vitro was catalysed by casein kinase II, cell division control 2 kinase (cdc2 kinase), protein kinases C alpha and beta II, and glycogen synthase kinase-3 (GSK-3), but not by mitogen-activated kinase (MAP kinase). Casein kinase II phosphorylation was directed exclusively to Ser-362. The sites phosphorylated by cdc2 kinase and GSK-3 were restricted to several serines within three proline-rich motifs of domain P. Sites phosphorylated in vitro by protein kinase C, on the other hand, were distributed over the N-terminal catalytic as well as the C-terminal regulatory domain. The stoichiometry of phosphorylation catalysed by any of these kinases was less than 0.2 mol P/mol CT, and no effects on enzyme activity were detected. This study supports a tripartite structure for CT with an N-terminal catalytic domain and a C-terminal regulatory domain comprised of a membrane-binding domain (domain M) and a phosphorylation domain (domain P). It also identifies three kinases as potential regulators in vivo of CT, casein kinase II, cyclin-dependent kinase and GSK-3.

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Galle, Lisa M., George E. Cutsail III, Volker Nischwitz, Serena DeBeer, and Ingrid Span. "Spectroscopic characterization of the Co-substituted C-terminal domain of rubredoxin-2." Biological Chemistry 399, no. 7 (June 27, 2018): 787–98. http://dx.doi.org/10.1515/hsz-2018-0142.

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Abstract Pseudomonas putida rubredoxin-2 (Rxn2) is an essential member of the alkane hydroxylation pathway and transfers electrons from a reductase to the membrane-bound hydroxylase. The regioselective hydroxylation of linear alkanes is a challenging chemical transformation of great interest for the chemical industry. Herein, we report the preparation and spectroscopic characterization of cobalt-substituted P. putida Rxn2 and a truncated version of the protein consisting of the C-terminal domain of the protein. Our spectroscopic data on the Co-substituted C-terminal domain supports a high-spin Co(II) with a distorted tetrahedral coordination environment. Investigation of the two-domain protein Rxn2 provides insights into the metal-binding properties of the N-terminal domain, the role of which is not well understood so far. Circular dichroism, electron paramagnetic resonance and X-ray absorption spectroscopies support an alternative Co-binding site within the N-terminal domain, which appears to not be relevant in nature. We have shown that chemical reconstitution in the presence of Co leads to incorporation of Co(II) into the active site of the C-terminal domain, but not the N-terminal domain of Rxn2 indicating distinct roles for the two rubredoxin domains.

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Bix, Gregory, Rex A. Iozzo, Ben Woodall, Michelle Burrows, Angela McQuillan, Shelly Campbell, Gregg B. Fields, and Renato V. Iozzo. "Endorepellin, the C-terminal angiostatic module of perlecan, enhances collagen-platelet responses via the α2β1-integrin receptor." Blood 109, no. 9 (December 29, 2006): 3745–48. http://dx.doi.org/10.1182/blood-2006-08-039925.

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Abstract Endorepellin, a C-terminal fragment of the vascular basement membrane proteoglycan perlecan, inhibits angiogenesis via the α2β1-integrin receptor. Because this integrin is also implicated in platelet-collagen responses and because endorepellin or its fragments are generated in response to injury and inflammation, we hypothesized that endorepellin could also affect platelet biology. We discovered that endorepellin supported α2β1-dependent platelet adhesion, without appreciably activating or aggregating platelets. Notably, endorepellin enhanced collagen-evoked responses in platelets, in a src kinase-dependent fashion, and enhanced the collagen-inhibitory effect of an α2β1-integrin function-blocking antibody. Collectively, these results suggest that endorepellin/α2β1-integrin interaction and effects are specific and dependent on cell type, differ from those emanated by exposure to collagen, and may be due to cellular differences in α2β1-integrin activation/ligand affinity state. These studies also suggest a heretofore unrecognized role for angiostatic basement membrane fragments in platelet biology.

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Taft-Benz, Sharon A., and Roel M. Schaaper. "The C-Terminal Domain of DnaQ Contains the Polymerase Binding Site." Journal of Bacteriology 181, no. 9 (May 1, 1999): 2963–65. http://dx.doi.org/10.1128/jb.181.9.2963-2965.1999.

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ABSTRACT The Escherichia coli dnaQ gene encodes the 3′→5′ exonucleolytic proofreading (ɛ) subunit of DNA polymerase III (Pol III). Genetic analysis of dnaQ mutants has suggested that ɛ might consist of two domains, an N-terminal domain containing the exonuclease and a C-terminal domain essential for binding the polymerase (α) subunit. We have created truncated forms ofdnaQ resulting in ɛ subunits that contain either the N-terminal or the C-terminal domain. Using the yeast two-hybrid system, we analyzed the interactions of the single-domain ɛ subunits with the α and θ subunits of the Pol III core. The DnaQ991 protein, consisting of the N-terminal 186 amino acids, was defective in binding to the α subunit while retaining normal binding to the θ subunit. In contrast, the NΔ186 protein, consisting of the C-terminal 57 amino acids, exhibited normal binding to the α subunit but was defective in binding to the θ subunit. A strain carrying the dnaQ991allele exhibited a strong, recessive mutator phenotype, as expected from a defective α binding mutant. The data are consistent with the existence of two functional domains in ɛ, with the C-terminal domain responsible for polymerase binding.

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Gianulis, Elena C., and Matthew Trudeau. "The hERG N-Terminal eag Domain Directly Interacts with the C-Terminal Cyclic Nucleotide-Binding Homology Domain." Biophysical Journal 104, no. 2 (January 2013): 356a. http://dx.doi.org/10.1016/j.bpj.2012.11.1979.

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45

Liefhebber, Jolanda MP, Bernd W. Brandt, Rene Broer, Willy JM Spaan, and Hans C. van Leeuwen. "Hepatitis C virus NS4B carboxy terminal domain is a membrane binding domain." Virology Journal 6, no. 1 (2009): 62. http://dx.doi.org/10.1186/1743-422x-6-62.

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46

Rufer, Arne C., Eric Kusznir, Dominique Burger, Martine Stihle, Armin Ruf, and Markus G. Rudolph. "Domain swap in the C-terminal ubiquitin-like domain of human doublecortin." Acta Crystallographica Section D Structural Biology 74, no. 5 (April 26, 2018): 450–62. http://dx.doi.org/10.1107/s2059798318004813.

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Doublecortin, a microtubule-associated protein that is only produced during neurogenesis, cooperatively binds to microtubules and stimulates microtubule polymerization and cross-linking by unknown mechanisms. A domain swap is observed in the crystal structure of the C-terminal domain of doublecortin. As determined by analytical ultracentrifugation, an open conformation is also present in solution. At higher concentrations, higher-order oligomers of the domain are formed. The domain swap and additional interfaces observed in the crystal lattice can explain the formation of doublecortin tetramers or multimers, in line with the analytical ultracentrifugation data. Taken together, the domain swap offers a mechanism for the observed cooperative binding of doublecortin to microtubules. Doublecortin-induced cross-linking of microtubules can be explained by the same mechanism. The effect of several mutations leading to lissencephaly and double-cortex syndrome can be traced to the domain swap and the proposed self-association of doublecortin.

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Shannon, Jennifer L., and Rachel C. Fernandez. "The C-Terminal Domain of the Bordetella pertussisAutotransporter BrkA Forms a Pore in Lipid Bilayer Membranes." Journal of Bacteriology 181, no. 18 (September 15, 1999): 5838–42. http://dx.doi.org/10.1128/jb.181.18.5838-5842.1999.

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ABSTRACT BrkA is a 103-kDa outer membrane protein of Bordetella pertussis that mediates resistance to antibody-dependent killing by complement. It is proteolytically processed into a 73-kDa N-terminal domain and a 30-kDa C-terminal domain as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. BrkA is also a member of the autotransporter family of proteins. Translocation of the N-terminal domain of the protein across the outer membrane is hypothesized to occur through a pore formed by the C-terminal domain. To test this hypothesis, we performed black lipid bilayer experiments with purified recombinant protein. The BrkA C-terminal protein showed an average single-channel conductance of 3.0 nS in 1 M KCl. This result strongly suggests that the C-terminal autotransporter domain of BrkA is indeed capable of forming a pore.

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Waclawska, Izabela, and Christine Ziegler. "Regulatory role of charged clusters in the N-terminal domain of BetP from Corynebacterium glutamicum." Biological Chemistry 396, no. 9-10 (September 1, 2015): 1117–26. http://dx.doi.org/10.1515/hsz-2015-0160.

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Abstract The trimeric transporter BetP counteracts hyperosmotic stress by a fast increase in transport rate in order to accumulate the compatible solute betaine. The positively charged α-helical C-terminal domain acts as an osmosensor perceiving the increase in the internal potassium (K+) concentration. A second, still unidentified stimulus originates from stress-induced changes in the physical state of the membrane and depends on the amount of negatively charged lipids. BetP possesses a 60-amino acid (aa)-long negatively charged N-terminal domain, which is predicted to adopt a partly helical fold affecting osmoregulation by an unknown mechanism. It is assumed that the C-terminal domain, the N-terminal domain, and negatively charged lipids interact during stress sensing and regulation. Here, we have investigated the regulatory role of negatively charged clusters in the N-terminal domain. We identified one cluster, Glu24Glu25, to be crucial for osmoregulation. Cross-linking studies revealed an interaction between the C- and N-terminal domains of adjacent protomers modulating transport activation. A regulatory partner-switching mechanism emerges in which the C-terminal domain changes its interaction with the N-terminal domain of its own promoter and negatively charged lipids to an interaction with the N-terminal domain of an adjacent protomer and lipids bound to the central cavity of the BetP trimer.

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Tanaka, M., W. M. Clouston, and W. Herr. "The Oct-2 glutamine-rich and proline-rich activation domains can synergize with each other or duplicates of themselves to activate transcription." Molecular and Cellular Biology 14, no. 9 (September 1994): 6046–55. http://dx.doi.org/10.1128/mcb.14.9.6046-6055.1994.

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The B-cell POU homeodomain protein Oct-2 contains two transcriptional activation domains, one N terminal and the other C terminal of the central DNA-binding POU domain. The synergistic action of these two activation domains makes Oct-2 a more potent activator of mRNA promoters than the related broadly expressed octamer motif-binding protein Oct-1, which contains an N-terminal but not a C-terminal Oct-2-like activation domain. Both Oct-2 mRNA promoter activation domains were delineated by truncation analysis: the N-terminal Q domain is a 66-amino-acid region rich in glutamines, and the C-terminal P domain is a 42-amino-acid region rich in prolines. The Q and P domains synergized with each other or duplicates of themselves, independently of their N-terminal or C-terminal position relative to the POU domain. The C-terminal P domain, which differentiates Oct-2 from Oct-1, also activated transcription in conjunction with the heterologous GAL4 DNA-binding domain. Oct-2 thus contains three modular functional units, the DNA-binding POU domain and the two P and Q activation domains. An electrophoretic mobility shift assay with a variety of these Oct-2 activators revealed a distinct complex called QA that was dependent on the presence of an active glutamine-rich activation domain and migrated more slowly than the Oct-2-DNA complexes. Formation of the QA complex is consistent with interaction of the glutamine-rich activation domains with a regulatory protein important for the process of transcriptional activation.

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50

Tanaka, M., W. M. Clouston, and W. Herr. "The Oct-2 glutamine-rich and proline-rich activation domains can synergize with each other or duplicates of themselves to activate transcription." Molecular and Cellular Biology 14, no. 9 (September 1994): 6046–55. http://dx.doi.org/10.1128/mcb.14.9.6046.

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The B-cell POU homeodomain protein Oct-2 contains two transcriptional activation domains, one N terminal and the other C terminal of the central DNA-binding POU domain. The synergistic action of these two activation domains makes Oct-2 a more potent activator of mRNA promoters than the related broadly expressed octamer motif-binding protein Oct-1, which contains an N-terminal but not a C-terminal Oct-2-like activation domain. Both Oct-2 mRNA promoter activation domains were delineated by truncation analysis: the N-terminal Q domain is a 66-amino-acid region rich in glutamines, and the C-terminal P domain is a 42-amino-acid region rich in prolines. The Q and P domains synergized with each other or duplicates of themselves, independently of their N-terminal or C-terminal position relative to the POU domain. The C-terminal P domain, which differentiates Oct-2 from Oct-1, also activated transcription in conjunction with the heterologous GAL4 DNA-binding domain. Oct-2 thus contains three modular functional units, the DNA-binding POU domain and the two P and Q activation domains. An electrophoretic mobility shift assay with a variety of these Oct-2 activators revealed a distinct complex called QA that was dependent on the presence of an active glutamine-rich activation domain and migrated more slowly than the Oct-2-DNA complexes. Formation of the QA complex is consistent with interaction of the glutamine-rich activation domains with a regulatory protein important for the process of transcriptional activation.

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Journal articles on the topic 'C-terminal domain of perlecan'

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