Journal articles: 'The N-end rule'

1

Varshavsky, A. "The N-end Rule." Cold Spring Harbor Symposia on Quantitative Biology 60 (January 1, 1995): 461–78. http://dx.doi.org/10.1101/sqb.1995.060.01.051.

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Varshavsky, Alexander. "The N-end rule." Cell 69, no. 5 (May 1992): 725–35. http://dx.doi.org/10.1016/0092-8674(92)90285-k.

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Tasaki, Takafumi, Shashikanth M. Sriram, Kyong Soo Park, and Yong Tae Kwon. "The N-End Rule Pathway." Annual Review of Biochemistry 81, no. 1 (July 7, 2012): 261–89. http://dx.doi.org/10.1146/annurev-biochem-051710-093308.

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Kim, Jeong-Mok, and Cheol-Sang Hwang. "Crosstalk between the Arg/N-end and Ac/N-end rule." Cell Cycle 13, no. 9 (April 3, 2014): 1366–67. http://dx.doi.org/10.4161/cc.28751.

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Tobias, J., T. Shrader, G. Rocap, and A. Varshavsky. "The N-end rule in bacteria." Science 254, no. 5036 (November 29, 1991): 1374–77. http://dx.doi.org/10.1126/science.1962196.

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Hurtley, Stella M. "Another N-end rule to add." Science 362, no. 6418 (November 29, 2018): 1014.11–1016. http://dx.doi.org/10.1126/science.362.6418.1014-k.

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Eldeeb, Mohamed, and Richard Fahlman. "The-N-End Rule: The Beginning Determines the End." Protein & Peptide Letters 23, no. 4 (March 1, 2016): 343–48. http://dx.doi.org/10.2174/0929866523666160108115809.

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Varshavsky, Alexander. "The N-end rule at atomic resolution." Nature Structural & Molecular Biology 15, no. 12 (December 2008): 1238–40. http://dx.doi.org/10.1038/nsmb1208-1238.

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Wojcik, Cezary. "Dipeptides: rulers of the N-end rule." Trends in Cell Biology 10, no. 9 (September 2000): 367. http://dx.doi.org/10.1016/s0962-8924(00)01827-4.

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Dougan, David A., and Alexander Varshavsky. "Understanding the Pro/N-end rule pathway." Nature Chemical Biology 14, no. 5 (April 16, 2018): 415–16. http://dx.doi.org/10.1038/s41589-018-0045-0.

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Varshavsky, A. "The N-end rule: functions, mysteries, uses." Proceedings of the National Academy of Sciences 93, no. 22 (October 29, 1996): 12142–49. http://dx.doi.org/10.1073/pnas.93.22.12142.

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Davydov, Ilia V., Debabrata Patra, and Alexander Varshavsky. "The N-End Rule Pathway inXenopusEgg Extracts." Archives of Biochemistry and Biophysics 357, no. 2 (September 1998): 317–25. http://dx.doi.org/10.1006/abbi.1998.0829.

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Eldeeb, Mohamed A., Luana C. A. Leitao, and Richard P. Fahlman. "Emerging branches of the N-end rule pathways are revealing the sequence complexities of N-termini dependent protein degradation." Biochemistry and Cell Biology 96, no. 3 (June 2018): 289–94. http://dx.doi.org/10.1139/bcb-2017-0274.

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Abstract:

The N-end rule links the identity of the N-terminal amino acid of a protein to its in vivo half-life, as some N-terminal residues confer metabolic instability to a protein via their recognition by the cellular machinery that targets them for degradation. Since its discovery, the N-end rule has generally been defined as set of rules of whether an N-terminal residue is stabilizing or not. However, recent studies are revealing that the N-terminal code of amino acids conferring protein instability is more complex than previously appreciated, as recent investigations are revealing that the identity of adjoining downstream residues can also influence the metabolic stability of N-end rule substrate. This is exemplified by the recent discovery of a new branch of N-end rule pathways that target proteins bearing N-terminal proline. In addition, recent investigations are demonstrating that the molecular machinery in N-termini dependent protein degradation may also target proteins for lysosomal degradation, in addition to proteasome-dependent degradation. Herein, we describe some of the recent advances in N-end rule pathways and discuss some of the implications regarding the emerging additional sequence requirements.

14

Madura, K., R. J. Dohmen, and A. Varshavsky. "N-recognin/Ubc2 interactions in the N-end rule pathway." Journal of Biological Chemistry 268, no. 16 (June 1993): 12046–54. http://dx.doi.org/10.1016/s0021-9258(19)50306-4.

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15

Sriram, Shashikanth M., and Yong Tae Kwon. "The molecular principles of N-end rule recognition." Nature Structural & Molecular Biology 17, no. 10 (October 2010): 1164–65. http://dx.doi.org/10.1038/nsmb1010-1164.

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16

Varshavsky, Alexander. "The N-end rule and regulation of apoptosis." Nature Cell Biology 5, no. 5 (May 2003): 373–76. http://dx.doi.org/10.1038/ncb0503-373.

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17

Kwon, Yong Tae, Frédéric Lévy, and Alexander Varshavsky. "Bivalent Inhibitor of the N-end Rule Pathway." Journal of Biological Chemistry 274, no. 25 (June 18, 1999): 18135–39. http://dx.doi.org/10.1074/jbc.274.25.18135.

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18

Varshavsky, Alexander. "The N-end rule pathway of protein degradation." Genes to Cells 2, no. 1 (January 1997): 13–28. http://dx.doi.org/10.1046/j.1365-2443.1997.1020301.x.

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19

Hurtley, Stella M. "The N-end rule finds a physiological function." Science Signaling 8, no. 368 (March 17, 2015): ec65-ec65. http://dx.doi.org/10.1126/scisignal.aab1180.

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20

Gonda, D. K., A. Bachmair, I. Wünning, J. W. Tobias, W. S. Lane, and A. Varshavsky. "Universality and Structure of the N-end Rule." Journal of Biological Chemistry 264, no. 28 (October 1989): 16700–16712. http://dx.doi.org/10.1016/s0021-9258(19)84762-2.

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21

Wang, Kevin H., Giselle Roman-Hernandez, Robert A. Grant, Robert T. Sauer, and Tania A. Baker. "The Molecular Basis of N-End Rule Recognition." Molecular Cell 32, no. 3 (November 2008): 406–14. http://dx.doi.org/10.1016/j.molcel.2008.08.032.

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22

Hurtley, S. M. "The N-end rule finds a physiological function." Science 347, no. 6227 (March 12, 2015): 1213. http://dx.doi.org/10.1126/science.347.6227.1213-q.

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23

Kim, Sung Tae, Takafumi Tasaki, Adriana Zakrzewska, Young Dong Yoo, Ki Sa Sung, Su-Hyeon Kim, Hyunjoo Cha-Molstad, et al. "The N-end rule proteolytic system in autophagy." Autophagy 9, no. 7 (July 11, 2013): 1100–1103. http://dx.doi.org/10.4161/auto.24643.

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24

VARSHAVSKY, A. "The N-end rule pathway: Functions and mechanisms." Cell Biology International Reports 14 (September 1990): 8. http://dx.doi.org/10.1016/0309-1651(90)90142-l.

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25

Merkel, Lars, Henning S. G. Beckmann, Valentin Wittmann, and Nediljko Budisa. "Efficient N-Terminal Glycoconjugation of Proteins by the N-End Rule." ChemBioChem 9, no. 8 (May 23, 2008): 1220–24. http://dx.doi.org/10.1002/cbic.200800050.

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26

Graciet, Emmanuelle, and Frank Wellmer. "The plant N-end rule pathway: structure and functions." Trends in Plant Science 15, no. 8 (August 2010): 447–53. http://dx.doi.org/10.1016/j.tplants.2010.04.011.

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27

Dougan, D. A., K. N. Truscott, and K. Zeth. "The bacterial N-end rule pathway: expect the unexpected." Molecular Microbiology 76, no. 3 (March 30, 2010): 545–58. http://dx.doi.org/10.1111/j.1365-2958.2010.07120.x.

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28

Yamano, Koji, and Richard J. Youle. "PINK1 is degraded through the N-end rule pathway." Autophagy 9, no. 11 (November 3, 2013): 1758–69. http://dx.doi.org/10.4161/auto.24633.

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29

Varshavsky, Alexander. "The N-end rule pathway and regulation by proteolysis." Protein Science 20, no. 8 (July 7, 2011): 1298–345. http://dx.doi.org/10.1002/pro.666.

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30

Bartel, B., I. Wünning, and A. Varshavsky. "The recognition component of the N-end rule pathway." EMBO Journal 9, no. 10 (October 1990): 3179–89. http://dx.doi.org/10.1002/j.1460-2075.1990.tb07516.x.

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31

Oh, Jang-Hyun, Ju-Yeon Hyun, and Alexander Varshavsky. "Control of Hsp90 chaperone and its clients by N-terminal acetylation and the N-end rule pathway." Proceedings of the National Academy of Sciences 114, no. 22 (May 17, 2017): E4370—E4379. http://dx.doi.org/10.1073/pnas.1705898114.

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Abstract:

We found that the heat shock protein 90 (Hsp90) chaperone system of the yeast Saccharomyces cerevisiae is greatly impaired in naa10Δ cells, which lack the NatA Nα-terminal acetylase (Nt-acetylase) and therefore cannot N-terminally acetylate a majority of normally N-terminally acetylated proteins, including Hsp90 and most of its cochaperones. Chk1, a mitotic checkpoint kinase and a client of Hsp90, was degraded relatively slowly in wild-type cells but was rapidly destroyed in naa10Δ cells by the Arg/N-end rule pathway, which recognized a C terminus-proximal degron of Chk1. Diverse proteins (in addition to Chk1) that are shown here to be targeted for degradation by the Arg/N-end rule pathway in naa10Δ cells include Kar4, Tup1, Gpd1, Ste11, and also, remarkably, the main Hsp90 chaperone (Hsc82) itself. Protection of Chk1 by Hsp90 could be overridden not only by ablation of the NatA Nt-acetylase but also by overexpression of the Arg/N-end rule pathway in wild-type cells. Split ubiquitin-binding assays detected interactions between Hsp90 and Chk1 in wild-type cells but not in naa10Δ cells. These and related results revealed a major role of Nt-acetylation in the Hsp90-mediated protein homeostasis, a strong up-regulation of the Arg/N-end rule pathway in the absence of NatA, and showed that a number of Hsp90 clients are previously unknown substrates of the Arg/N-end rule pathway.

32

Siepmann, Thomas J., Richard N. Bohnsack, Zeynep Tokgöz, Olga V. Baboshina, and Arthur L. Haas. "Protein Interactions within the N-end Rule Ubiquitin Ligation Pathway." Journal of Biological Chemistry 278, no. 11 (January 10, 2003): 9448–57. http://dx.doi.org/10.1074/jbc.m211240200.

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33

Baker, R. T., and A. Varshavsky. "Inhibition of the N-end rule pathway in living cells." Proceedings of the National Academy of Sciences 88, no. 4 (February 15, 1991): 1090–94. http://dx.doi.org/10.1073/pnas.88.4.1090.

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34

Madura, K., and A. Varshavsky. "Degradation of G alpha by the N-end rule pathway." Science 265, no. 5177 (September 2, 1994): 1454–58. http://dx.doi.org/10.1126/science.8073290.

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35

Hu, R. G., H. Wang, Z. Xia, and A. Varshavsky. "The N-end rule pathway is a sensor of heme." Proceedings of the National Academy of Sciences 105, no. 1 (December 27, 2007): 76–81. http://dx.doi.org/10.1073/pnas.0710568105.

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36

Tasaki, Takafumi, Adriana Zakrzewska, Drew D. Dudgeon, Yonghua Jiang, John S. Lazo, and Yong Tae Kwon. "The Substrate Recognition Domains of the N-end Rule Pathway." Journal of Biological Chemistry 284, no. 3 (November 13, 2008): 1884–95. http://dx.doi.org/10.1074/jbc.m803641200.

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37

Kim, Jeong-Mok, Ok-Hee Seok, Shinyeong Ju, Ji-Eun Heo, Jeonghun Yeom, Da-Som Kim, Joo-Yeon Yoo, Alexander Varshavsky, Cheolju Lee, and Cheol-Sang Hwang. "Formyl-methionine as an N-degron of a eukaryotic N-end rule pathway." Science 362, no. 6418 (November 8, 2018): eaat0174. http://dx.doi.org/10.1126/science.aat0174.

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In bacteria, nascent proteins bear the pretranslationally generated N-terminal (Nt) formyl-methionine (fMet) residue. Nt-fMet of bacterial proteins is a degradation signal, termed fMet/N-degron. By contrast, proteins synthesized by cytosolic ribosomes of eukaryotes were presumed to bear unformylated Nt-Met. Here we found that the yeast formyltransferase Fmt1, although imported into mitochondria, could also produce Nt-formylated proteins in the cytosol. Nt-formylated proteins were strongly up-regulated in stationary phase or upon starvation for specific amino acids. This up-regulation strictly required the Gcn2 kinase, which phosphorylates Fmt1 and mediates its retention in the cytosol. We also found that the Nt-fMet residues of Nt-formylated proteins act as fMet/N-degrons and identified the Psh1 ubiquitin ligase as the recognition component of the eukaryotic fMet/N-end rule pathway, which destroys Nt-formylated proteins.

38

Wang, Haiqing, Konstantin I. Piatkov, Christopher S. Brower, and Alexander Varshavsky. "Glutamine-Specific N-Terminal Amidase, a Component of the N-End Rule Pathway." Molecular Cell 34, no. 6 (June 2009): 686–95. http://dx.doi.org/10.1016/j.molcel.2009.04.032.

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39

Kwon, Yong Tae, Zanxian Xia, Ilia V. Davydov, Stewart H. Lecker, and Alexander Varshavsky. "Construction and Analysis of Mouse Strains Lacking the Ubiquitin Ligase UBR1 (E3α) of the N-End Rule Pathway." Molecular and Cellular Biology 21, no. 23 (December 1, 2001): 8007–21. http://dx.doi.org/10.1128/mcb.21.23.8007-8021.2001.

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ABSTRACT The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. In the yeast Saccharomyces cerevisiae, the UBR1-encoded ubiquitin ligase (E3) of the N-end rule pathway mediates the targeting of substrate proteins in part through binding to their destabilizing N-terminal residues. The functions of the yeast N-end rule pathway include fidelity of chromosome segregation and the regulation of peptide import. Our previous work described the cloning of cDNA and a gene encoding the 200-kDa mouse UBR1 (E3α). Here we show that mouse UBR1, in the presence of a cognate mouse ubiquitin-conjugating (E2) enzyme, can rescue the N-end rule pathway in ubr1Δ S. cerevisiae. We also constructedUBR1 −/− mouse strains that lacked the UBR1 protein. UBR1 −/− mice were viable and fertile but weighed significantly less than congenic +/+ mice. The decreased mass of UBR1 −/− mice stemmed at least in part from smaller amounts of the skeletal muscle and adipose tissues. The skeletal muscle of UBR1 −/−mice apparently lacked the N-end rule pathway and exhibited abnormal regulation of fatty acid synthase upon starvation. By contrast, and despite the absence of the UBR1 protein,UBR1 −/− fibroblasts contained the N-end rule pathway. Thus, UBR1 −/− mice are mosaics in regard to the activity of this pathway, owing to differential expression of proteins that can substitute for the ubiquitin ligase UBR1 (E3α). We consider these UBR1-like proteins and discuss the functions of the mammalian N-end rule pathway.

40

Eldeeb, Mohamed, Richard Fahlman, Mansoore Esmaili, and Mohamed Ragheb. "Regulating Apoptosis by Degradation: The N-End Rule-Mediated Regulation of Apoptotic Proteolytic Fragments in Mammalian Cells." International Journal of Molecular Sciences 19, no. 11 (October 31, 2018): 3414. http://dx.doi.org/10.3390/ijms19113414.

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A pivotal hallmark of some cancer cells is the evasion of apoptotic cell death. Importantly, the initiation of apoptosis often results in the activation of caspases, which, in turn, culminates in the generation of proteolytically-activated protein fragments with potentially new or altered roles. Recent investigations have revealed that the activity of a significant number of the protease-generated, activated, pro-apoptotic protein fragments can be curbed via their selective degradation by the N-end rule degradation pathways. Of note, previous work revealed that several proteolytically-generated, pro-apoptotic fragments are unstable in cells, as their destabilizing N-termini target them for proteasomal degradation via the N-end rule degradation pathways. Remarkably, previous studies also showed that the proteolytically-generated anti-apoptotic Lyn kinase protein fragment is targeted for degradation by the UBR1/UBR2 E3 ubiquitin ligases of the N-end rule pathway in chronic myeloid leukemia cells. Crucially, the degradation of cleaved fragment of Lyn by the N-end rule counters imatinib resistance in these cells, implicating a possible linkage between the N-end rule degradation pathway and imatinib resistance. Herein, we highlight recent studies on the role of the N-end rule proteolytic pathways in regulating apoptosis in mammalian cells, and also discuss some possible future directions with respect to apoptotic proteolysis signaling.

41

Wadas, Brandon, Jimo Borjigin, Zheping Huang, Jang-Hyun Oh, Cheol-Sang Hwang, and Alexander Varshavsky. "Degradation of SerotoninN-Acetyltransferase, a Circadian Regulator, by the N-end Rule Pathway." Journal of Biological Chemistry 291, no. 33 (June 23, 2016): 17178–96. http://dx.doi.org/10.1074/jbc.m116.734640.

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SerotoninN-acetyltransferase (AANAT) converts serotonin toN-acetylserotonin (NAS), a distinct biological regulator and the immediate precursor of melatonin, a circulating hormone that influences circadian processes, including sleep. N-terminal sequences of AANAT enzymes vary among vertebrates. Mechanisms that regulate the levels of AANAT are incompletely understood. Previous findings were consistent with the possibility that AANAT may be controlled through its degradation by the N-end rule pathway. By expressing the rat and human AANATs and their mutants not only in mammalian cells but also in the yeastSaccharomyces cerevisiae, and by taking advantage of yeast genetics, we show here that two “complementary” forms of rat AANAT are targeted for degradation by two “complementary” branches of the N-end rule pathway. Specifically, the Nα-terminally acetylated (Nt-acetylated) Ac-AANAT is destroyed through the recognition of its Nt-acetylated N-terminal Met residue by the Ac/N-end rule pathway, whereas the non-Nt-acetylated AANAT is targeted by the Arg/N-end rule pathway, which recognizes the unacetylated N-terminal Met-Leu sequence of rat AANAT. We also show, by constructing lysine-to-arginine mutants of rat AANAT, that its degradation is mediated by polyubiquitylation of its Lys residue(s). Human AANAT, whose N-terminal sequence differs from that of rodent AANATs, is longer-lived than its rat counterpart and appears to be refractory to degradation by the N-end rule pathway. Together, these and related results indicate both a major involvement of the N-end rule pathway in the control of rodent AANATs and substantial differences in the regulation of rodent and human AANATs that stem from differences in their N-terminal sequences.

42

Nguyen, Kha The, Sang-Hyeon Mun, Chang-Seok Lee, and Cheol-Sang Hwang. "Control of protein degradation by N-terminal acetylation and the N-end rule pathway." Experimental & Molecular Medicine 50, no. 7 (July 2018): 1–8. http://dx.doi.org/10.1038/s12276-018-0097-y.

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43

Mulder, Lubbertus C. F., and Mark A. Muesing. "Degradation of HIV-1 Integrase by the N-end Rule Pathway." Journal of Biological Chemistry 275, no. 38 (July 12, 2000): 29749–53. http://dx.doi.org/10.1074/jbc.m004670200.

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44

Graciet, Emmanuelle, Francesca Mesiti, and Frank Wellmer. "Structure and evolutionary conservation of the plant N-end rule pathway." Plant Journal 61, no. 5 (March 2010): 741–51. http://dx.doi.org/10.1111/j.1365-313x.2009.04099.x.

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45

Gibbs, Daniel J., Jaume Bacardit, Andreas Bachmair, and Michael J. Holdsworth. "The eukaryotic N-end rule pathway: conserved mechanisms and diverse functions." Trends in Cell Biology 24, no. 10 (October 2014): 603–11. http://dx.doi.org/10.1016/j.tcb.2014.05.001.

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46

Liu, Yujiao, Chao Liu, Wen Dong, and Wei Li. "Physiological functions and clinical implications of the N-end rule pathway." Frontiers of Medicine 10, no. 3 (September 2016): 258–70. http://dx.doi.org/10.1007/s11684-016-0458-7.

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47

Boso, Guney, Takafumi Tasaki, Yong Kwon, and Nikunj V. Somia. "The N-end rule and retroviral infection: no effect on integrase." Virology Journal 10, no. 1 (2013): 233. http://dx.doi.org/10.1186/1743-422x-10-233.

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48

Wang, Kevin H., Elizabeth S. C. Oakes, Robert T. Sauer, and Tania A. Baker. "Tuning the Strength of a Bacterial N-end Rule Degradation Signal." Journal of Biological Chemistry 283, no. 36 (June 11, 2008): 24600–24607. http://dx.doi.org/10.1074/jbc.m802213200.

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49

Lin, Chih-Cheng, Ya-Ting Chao, Wan-Chieh Chen, Hsiu-Yin Ho, Mei-Yi Chou, Ya-Ru Li, Yu-Lin Wu, et al. "Regulatory cascade involving transcriptional and N-end rule pathways in rice under submergence." Proceedings of the National Academy of Sciences 116, no. 8 (February 5, 2019): 3300–3309. http://dx.doi.org/10.1073/pnas.1818507116.

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The rice SUB1A-1 gene, which encodes a group VII ethylene response factor (ERFVII), plays a pivotal role in rice survival under flooding stress, as well as other abiotic stresses. In Arabidopsis, five ERFVII factors play roles in regulating hypoxic responses. A characteristic feature of Arabidopsis ERFVIIs is a destabilizing N terminus, which functions as an N-degron that targets them for degradation via the oxygen-dependent N-end rule pathway of proteolysis, but permits their stabilization during hypoxia for hypoxia-responsive signaling. Despite having the canonical N-degron sequence, SUB1A-1 is not under N-end rule regulation, suggesting a distinct hypoxia signaling pathway in rice during submergence. Herein we show that two other rice ERFVIIs gene, ERF66 and ERF67, are directly transcriptionally up-regulated by SUB1A-1 under submergence. In contrast to SUB1A-1, ERF66 and ERF67 are substrates of the N-end rule pathway that are stabilized under hypoxia and may be responsible for triggering a stronger transcriptional response to promote submergence survival. In support of this, overexpression of ERF66 or ERF67 leads to activation of anaerobic survival genes and enhanced submergence tolerance. Furthermore, by using structural and protein-interaction analyses, we show that the C terminus of SUB1A-1 prevents its degradation via the N-end rule and directly interacts with the SUB1A-1 N terminus, which may explain the enhanced stability of SUB1A-1 despite bearing an N-degron sequence. In summary, our results suggest that SUB1A-1, ERF66, and ERF67 form a regulatory cascade involving transcriptional and N-end rule control, which allows rice to distinguish flooding from other SUB1A-1–regulated stresses.

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Chui, Ashley J., Marian C. Okondo, Sahana D. Rao, Kuo Gai, Andrew R. Griswold, Darren C. Johnson, Daniel P. Ball, et al. "N-terminal degradation activates the NLRP1B inflammasome." Science 364, no. 6435 (March 14, 2019): 82–85. http://dx.doi.org/10.1126/science.aau1208.

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Intracellular pathogens and danger signals trigger the formation of inflammasomes, which activate inflammatory caspases and induce pyroptosis. The anthrax lethal factor metalloprotease and small-molecule DPP8/9 inhibitors both activate the NLRP1B inflammasome, but the molecular mechanism of NLRP1B activation is unknown. In this study, we used genome-wide CRISPR-Cas9 knockout screens to identify genes required for NLRP1B-mediated pyroptosis. We discovered that lethal factor induces cell death via the N-end rule proteasomal degradation pathway. Lethal factor directly cleaves NLRP1B, inducing the N-end rule–mediated degradation of the NLRP1B N terminus and freeing the NLRP1B C terminus to activate caspase-1. DPP8/9 inhibitors also induce proteasomal degradation of the NLRP1B N terminus but not via the N-end rule pathway. Thus, N-terminal degradation is the common activation mechanism of this innate immune sensor.

Journal articles on the topic 'The N-end rule'

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