Relevant bibliographies by topics / CDK17

Academic literature on the topic 'CDK17'

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Published: 1 April 2023

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Journal articles on the topic "CDK17"

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Liu, Mingfa, Zhennan Xu, Zepeng Du, Bingli Wu, Tao Jin, Ke Xu, Liyan Xu, Enmin Li, and Haixiong Xu. "The Identification of Key Genes and Pathways in Glioma by Bioinformatics Analysis." Journal of Immunology Research 2017 (2017): 1–9. http://dx.doi.org/10.1155/2017/1278081.

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Glioma is the most common malignant tumor in the central nervous system. This study aims to explore the potential mechanism and identify gene signatures of glioma. The glioma gene expression profile GSE4290 was analyzed for differentially expressed genes (DEGs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were applied for the enriched pathways. A protein-protein interaction (PPI) network was constructed to find the hub genes. Survival analysis was conducted to screen and validate critical genes. In this study, 775 downregulated DEGs were identified. GO analysis demonstrated that the DEGs were enriched in cellular protein modification, regulation of cell communication, and regulation of signaling. KEGG analysis indicated that the DEGs were enriched in the MAPK signaling pathway, endocytosis, oxytocin signaling, and calcium signaling. PPI network and module analysis found 12 hub genes, which were enriched in synaptic vesicle cycling rheumatoid arthritis and collecting duct acid secretion. The four key genes CDK17, GNA13, PHF21A, and MTHFD2 were identified in both generation (GSE4412) and validation (GSE4271) dataset, respectively. Regression analysis showed that CDK13, PHF21A, and MTHFD2 were independent predictors. The results suggested that CDK17, GNA13, PHF21A, and MTHFD2 might play important roles and potentially be valuable in the prognosis and treatment of glioma.
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Liang, Kaiwei, Xin Gao, Joshua M. Gilmore, Laurence Florens, Michael P. Washburn, Edwin Smith, and Ali Shilatifard. "Characterization of Human Cyclin-Dependent Kinase 12 (CDK12) and CDK13 Complexes in C-Terminal Domain Phosphorylation, Gene Transcription, and RNA Processing." Molecular and Cellular Biology 35, no. 6 (January 5, 2015): 928–38. http://dx.doi.org/10.1128/mcb.01426-14.

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Cyclin-dependent kinase 9 (CDK9) and CDK12 have each been demonstrated to phosphorylate the RNA polymerase II C-terminal domain (CTD) at serine 2 of the heptad repeat, both in vitro and in vivo . CDK9, as part of P-TEFb and the super elongation complex (SEC), is by far the best characterized of CDK9, CDK12, and CDK13. We employed both in vitro and in vivo assays to further investigate the molecular properties of CDK12 and its paralog CDK13. We isolated Flag-tagged CDK12 and CDK13 and found that they associate with numerous RNA processing factors. Although knockdown of CDK12, CDK13, or their cyclin partner CCNK did not affect the bulk CTD phosphorylation levels in HCT116 cells, transcriptome sequencing (RNA-seq) analysis revealed that CDK12 and CDK13 losses in HCT116 cells preferentially affect expression of DNA damage response and snoRNA genes, respectively. CDK12 and CDK13 depletion also leads to a loss of expression of RNA processing factors and to defects in RNA processing. These findings suggest that in addition to implementing CTD phosphorylation, CDK12 and CDK13 may affect RNA processing through direct physical interactions with RNA processing factors and by regulating their expression.
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Lier, S., I. Rein, S. Lund, A. Lång, E. Lång, N. Meyer, A. Dutta, et al. "P10.12.A CDK12/CDK13 inhibition disrupts a transcriptional program critical for glioblastoma survival." Neuro-Oncology 24, Supplement_2 (September 1, 2022): ii51. http://dx.doi.org/10.1093/neuonc/noac174.177.

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Abstract Background Glioblastoma multiforme (GBM) is the most prevalent and aggressive malignant tumor of the central nervous system. With a median survival of only one year, GBM patients have a particularly poor prognosis, highlighting a clear need for novel therapeutic strategies to target this disease. Transcriptional cyclin-dependent kinases (CDK), which phosphorylate key residues of RNA polymerase II (RNAPII) C-terminal domain (CTD), play a major role in sustaining aberrant transcriptional programs that are key to development and maintenance of cancer cells. Material and Methods We used pharmacological inhibition and genetic ablation to study effects of CDK12/CDK13 depletion on the proliferatory and migratory capacity of GBM cells and mouse xenografts. SLAM-seq, CUT&RUN and cell cycle assays were used to study the mechanistic effects of CDK12/CDK13 depletion in GBM cells. Results CDK12/CDK13 depletion markedly reduced the proliferatory and migratory capacity of GBM cells, as well as in vivo growth. CDK12/CDK13 inhibition potentiated existing chemotherapeutic treatments. Mechanistically, inhibition of CDK12/CDK13 leads to a genome-wide abrogation of RNAPII CTD phosphorylation, which in turn disrupts transcription and cell cycle progression in GBM cells. Conclusion These results provide proof-of-concept for the potential of CDK12 and CDK13 as therapeutic targets for GBM.
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Kohoutek, Jiri, and Dalibor Blazek. "Cyclin K goes with Cdk12 and Cdk13." Cell Division 7, no. 1 (2012): 12. http://dx.doi.org/10.1186/1747-1028-7-12.

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Fan, Zheng, Jennifer R. Devlin, Simon J. Hogg, Maria A. Doyle, Paul F. Harrison, Izabela Todorovski, Leonie A. Cluse, et al. "CDK13 cooperates with CDK12 to control global RNA polymerase II processivity." Science Advances 6, no. 18 (April 29, 2020): eaaz5041. http://dx.doi.org/10.1126/sciadv.aaz5041.

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The RNA polymerase II (POLII)–driven transcription cycle is tightly regulated at distinct checkpoints by cyclin-dependent kinases (CDKs) and their cognate cyclins. The molecular events underpinning transcriptional elongation, processivity, and the CDK-cyclin pair(s) involved remain poorly understood. Using CRISPR-Cas9 homology-directed repair, we generated analog-sensitive kinase variants of CDK12 and CDK13 to probe their individual and shared biological and molecular roles. Single inhibition of CDK12 or CDK13 induced transcriptional responses associated with cellular growth signaling pathways and/or DNA damage, with minimal effects on cell viability. In contrast, dual kinase inhibition potently induced cell death, which was associated with extensive genome-wide transcriptional changes including widespread use of alternative 3′ polyadenylation sites. At the molecular level, dual kinase inhibition resulted in the loss of POLII CTD phosphorylation and greatly reduced POLII elongation rates and processivity. These data define substantial redundancy between CDK12 and CDK13 and identify both as fundamental regulators of global POLII processivity and transcription elongation.
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Shah, Muzna, Muhammad Fazal Hussain Qureshi, Danish Mohammad, Mahira Lakhani, Tabinda Urooj, and Shamim Mushtaq. "CDKs family -a glimpse into the past and present: from cell cycle control to current biological functions." Asian Pacific Journal of Cancer Biology 5, no. 1 (February 25, 2020): 1–9. http://dx.doi.org/10.31557/apjcb.2020.5.1.1-9.

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Cyclin-dependent kinases (CDKs) are the catalytic subunits or protein kinases characterized by separate subunit “cyclin” that are essential for their enzymatic activity. CDKs play important roles in the control of cell cycle progression, cell division, neuronal function, epigenetic regulation, metabolism, stem cell renewal and transcription. However, they can accomplish some of these tasks independently, without binding with cyclin protein or kinase activity. Thus, so far, twenty different CDKs and cyclins have been reported in mammalian cells. The evolutionary expansion of the CDK family in mammals led to the division of CDKs into three cell-cycle-related subfamilies (Cdk1, Cdk4 and Cdk5) and five transcriptional subfamilies (Cdk7, Cdk8, Cdk9, Cdk11 and Cdk20). In this review, we summarizes that how CDKs are traditionally involve their latest revelations, their functional diversity beyond cell cycle regulation and their impact on development of disease in mammals.
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Zhang, Bo, Xuelin Zhong, Moira Sauane, Yihong Zhao, and Zhi-Liang Zheng. "Modulation of the Pol II CTD Phosphorylation Code by Rac1 and Cdc42 Small GTPases in Cultured Human Cancer Cells and Its Implication for Developing a Synthetic-Lethal Cancer Therapy." Cells 9, no. 3 (March 4, 2020): 621. http://dx.doi.org/10.3390/cells9030621.

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Rho GTPases, including Rho, Cdc42, Rac and ROP subfamilies, are key signaling molecules in RNA polymerase II (Pol II) transcriptional control. Our prior work has shown that plant ROP and yeast Cdc42 GTPases similarly modulate Ser2 and Ser5 phosphorylation status of the C-terminal domain (CTD) of the Pol II largest subunit by regulating CTD phosphatase degradation. Here, we present genetic and pharmacological evidence showing that Cdc42 and Rac1 GTPase signaling modulates a similar CTD Ser2 and Ser5 phosphorylation code in cultured human cancer cells. While siRNA knockdown of Cdc42 and Rac1, respectively, in HeLa cells increased the level of CTD Ser phosphatases RPAP2 and FCP1, they both decreased the level of CTD kinases CDK7 and CDK13. In addition, the protein degradation inhibitor MG132 reversed the effect of THZ1, a CDK7 inhibitor which could decrease the cell number and amount of CDK7 and CDK13, accompanied by a reduction in the level of CTD Ser2 and Ser5 phosphorylation and DOCK4 and DOCK9 (the activators for Rac1 and Cdc42, respectively). Conversely, treatments of Torin1 or serum deprivation, both of which promote protein degradation, could enhance the effect of THZ1, indicating the involvement of protein degradation in controlling CDK7 and CDK13. Our results support an evolutionarily conserved signaling shortcut model linking Rho GTPases to Pol II transcription across three kingdoms, Fungi, Plantae and Animalia, and could lead to the development of a potential synthetic-lethal strategy in controlling cancer cell proliferation or death.
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Guiro, Joana, Mathias Fagbemi, Michael Tellier, Justyna Zaborowska, Stephanie Barker, Marjorie Fournier, and Shona Murphy. "CAPTURE of the Human U2 snRNA Genes Expands the Repertoire of Associated Factors." Biomolecules 12, no. 5 (May 14, 2022): 704. http://dx.doi.org/10.3390/biom12050704.

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In order to identify factors involved in transcription of human snRNA genes and 3′ end processing of the transcripts, we have carried out CRISPR affinity purification in situ of regulatory elements (CAPTURE), which is deadCas9-mediated pull-down, of the tandemly repeated U2 snRNA genes in human cells. CAPTURE enriched many factors expected to be associated with these human snRNA genes including RNA polymerase II (pol II), Cyclin-Dependent Kinase 7 (CDK7), Negative Elongation Factor (NELF), Suppressor of Ty 5 (SPT5), Mediator 23 (MED23) and several subunits of the Integrator Complex. Suppressor of Ty 6 (SPT6); Cyclin K, the partner of Cyclin-Dependent Kinase 12 (CDK12) and Cyclin-Dependent Kinase 13 (CDK13); and SWI/SNF chromatin remodelling complex-associated SWI/SNF-related, Matrix-associated, Regulator of Chromatin (SMRC) factors were also enriched. Several polyadenylation factors, including Cleavage and Polyadenylation Specificity Factor 1 (CPSF1), Cleavage Stimulation Factors 1 and 2 (CSTF1,and CSTF2) were enriched by U2 gene CAPTURE. We have already shown by chromatin immunoprecipitation (ChIP) that CSTF2—and Pcf11 and Ssu72, which are also polyadenylation factors—are associated with the human U1 and U2 genes. ChIP-seq and ChIP-qPCR confirm the association of SPT6, Cyclin K, and CDK12 with the U2 genes. In addition, knockdown of SPT6 causes loss of subunit 3 of the Integrator Complex (INTS3) from the U2 genes, indicating a functional role in snRNA gene expression. CAPTURE has therefore expanded the repertoire of transcription and RNA processing factors associated with these genes and helped to identify a functional role for SPT6.
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Quereda, Victor, Simon Bayle, Francesca Vena, Sylvia M. Frydman, Andrii Monastyrskyi, William R. Roush, and Derek R. Duckett. "Therapeutic Targeting of CDK12/CDK13 in Triple-Negative Breast Cancer." Cancer Cell 36, no. 5 (November 2019): 545–58. http://dx.doi.org/10.1016/j.ccell.2019.09.004.

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Zhang, Tinghu, Nicholas Kwiatkowski, Calla M. Olson, Sarah E. Dixon-Clarke, Brian J. Abraham, Ann K. Greifenberg, Scott B. Ficarro, et al. "Covalent targeting of remote cysteine residues to develop CDK12 and CDK13 inhibitors." Nature Chemical Biology 12, no. 10 (August 29, 2016): 876–84. http://dx.doi.org/10.1038/nchembio.2166.

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Dissertations / Theses on the topic "CDK17"

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Dust, Sofia [Verfasser]. "Biochemical characterization, regulation, and inhibition of human transcription kinases CDK12 and CDK13 and human cell cycle-related kinase CDK14 / Sofia Dust." Bonn : Universitäts- und Landesbibliothek Bonn, 2019. http://d-nb.info/1223538028/34.

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Lianga, Noel. "Cdk1 Regulates Anaphase Onset." Thesis, Université d'Ottawa / University of Ottawa, 2014. http://hdl.handle.net/10393/31860.

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Cdk1 is an important cell cycle regulator that, in association with different cyclin regulatory subunits, is responsible for signaling important cell cycle events in all eukaryotic cells. In budding yeast, inhibition of Cdk1 by selective deletion of cyclin subunits has been shown to prevent anaphase onset, suggesting that Cdk1 activity is critically important for triggering anaphase onset. In many eukaryotes, Cdk1 has been shown to phosphorylate subunits of the anaphase promoting complex (APC), an E3 ubiquitin ligase which directly signals anaphase onset by triggering the degradation of the anaphase inhibitor securin. It is currently unclear, however, whether the APC is the sole essential substrate of Cdk1 in anaphase onset or if Cdk1 triggers anaphase onset by phosphorylating additional proteins. Eukaryotic Cdk1 is regulated by the Wee1 family of tyrosine kinases and the Cdc25 family of phosphatases which directly oppose Wee1 activity. Wee1 phosphorylation of Cdk1 on a single tyrosine residue inhibits Cdk1 and has been shown to prevent or delay mitotic entry. In this work we sought to further elucidate the mechanism through which Cdk1 regulates anaphase onset. We showed that, in addition to regulating mitotic entry, the budding yeast Wee1 kinase and Cdc25 phosphatase (Swe1 and Mih1 respectively in S. cerevisiae) regulate anaphase onset by modulating Cdk1 activity. Activation of Swe1 delays anaphase onset and cells lacking SWE1 enter anaphase prematurely, demonstrating that Swe1 regulates anaphase onset in unperturbed cell cycles. Deletion of the CDC55 regulatory subunit of PP2A has been shown to bypass cell cycle delays due to Swe1 activation. We showed that this is due, in part, to PP2ACdc55 dephosphorylation of Cdk1 sites on the APC. We have also shown that Cdk1 directly phosphorylates separase, the protease that dissolves sister chromatid linkages upon release from inhibitory securin/separase complexes upon APC-mediated securin degradation. Similar to phosphoregulation of the APC, we showed that Cdk1 phosphorylation of separase is opposed by PP2ACdc55. Phosphoregulation of separase appears to be important for regulation of the separase substrate Slk19 which cooperates with the conserved kinesin-5 Cin8 and microtubule bundling protein Ase1 to regulate spindle elongation at the spindle midzone.
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Chun, Stella Soyoung. "Identification and validation of CDK13 interacting proteins." Thesis, University of British Columbia, 2012. http://hdl.handle.net/2429/43130.

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Cyclin dependent kinases (CDKs) are components of signal transduction pathways that regulate cellular functions by phosphorylation of substrate proteins in response to upstream signals. The kinase domains of CDK12 and CDK13 are most similar to CDK9; CDK9 phosphorylates the C terminal domain (CTD) of RNA Polymerase II in order to stimulate processive transcription elongation. However, while most human CDKs consist of little more than a kinase domain, CDK12 and CDK13 are much larger and have several protein-protein interaction domains suggesting that they could participate within regulatory cascades. They also have a RS domain found in the SR protein family of splicing factors. Consistent with these features CDK12 and CDK13 co-localize with splicing factors and RNA Polymerase II in nuclear speckles. Based on these features CDK12 and CDK13 have been proposed to coordinately regulate splicing and transcription. Consistent with this hypothesis, both kinases phosphorylate the CTD of RNA polymerase II and regulate the alternative splicing of the Adenovirus E1a mini-gene model substrate. CDK12 has been found to interact with the splicing factors PRP19, CDC5L, RBM25, FBP11 and SRP55. Due to the similarity of CDK13 to CDK12, I investigated the interacting partners of CDK13 by immunoprecipitation and mass spectrometry and determined that CDK13 interacts with same splicing factors as CDK12. These interactions were validated by immunoprecipitation – western blot analysis. My results also indicated that PRP19 and CDC5L interact as a complex with CDK13. Therefore, the protein interaction partners of CDK13 and CDK12 suggest functional mechanisms for their ability to regulate splicing. In parallel projects, to begin investigating the functional roles of the kinase domain of CDK12 I constructed and expressed different CDK12 mutants in insect cells and in mammalian cells. Also to investigate the role of the CDK12 mutants and the protein-protein interactions of CDK13 in alternative splicing, I also developed a PCR based E1A mini-gene splicing assay.
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Moreira, Juliana. "Expressão e purificação da quinase dependente de ciclina 13 humana em sistema bacteriano." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/75/75133/tde-28082014-135313/.

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As quinases dependentes de ciclinas são proteínas que podem ser divididas de acordo com a sua atuação no ciclo celular ou no controle transcricional, elas se tornam ativas em determinadas etapas do ciclo celular dependendo do seu grau de fosforilação e de sua ligação com ciclinas e proteínas inibitórias, e exercem sua função fosforilando outras proteínas envolvidas no ciclo de divisão celular e transcrição influenciando suas atividades, garantindo que cada processo do ciclo ocorra em uma sequência ordenada. A CDK13 faz parte da família de proteínas quinases dependentes de ciclina, pode se ligar a ciclinas do tipo L ou K, regula os eventos de \"splicing\" alternativo, e interage com a proteína Tat do vírus HIV atuando como um possível fator de restrição, sendo que sua superexpressão diminui a produção de algumas proteínas virais suprimindo a produção do vírus. O DNA referente à CDK13 é replicado em células cancerosas, principalmente dos tipos hepático e cólon e reto, sendo um alvo para inibidores para tratamento de câncer. A fim de contribuir para o estudo dessa proteína, o projeto tem como objetivo expressá-la utilizando métodos de tecnologia de DNA recombinante. A sequência de DNA referente à CDK13 foi amplificada pela reação em cadeia da polimerase, após sua purificação, foi inserida no vetor pCR-Blunt e clonada em células de E. coli DH5α competentes. Porém, o DNA não foi liberado pela reação com as enzimas de restrição BamHI e NdeI. As bactérias Rosetta(DE3) transformadas com um plasmídeo sintético e crescidas em meio de auto-indução expressaram a CDK13. Após lise celular e purificação em coluna de Ni2+, a proteína foi detectada por Western Blot. Já as bactérias Rosetta(DE3) transformadas com o plasmídeo sintético modificado (o qual compreende a região do DNA que expressa o bolsão de ligação da CDK13), e induzidas em meio LB expressaram a CDK13, porém não foi possível purificá-la em coluna de afinidade ao Ni2+.
The cyclin-dependent kinases are proteins that can be classified by their function in the cell cycle or transcriptional control. They are activated in particular steps of the cell cycle depending on their phosphorylation degree, cyclin binding and inhibitory proteins. They act phosphorylating other proteins involved in the cell cycle and transcriptional control, influencing in their activities, ensuring that each step of the cell cycle occur in an ordered sequence. The CDK13 is one of the cyclin-dependent kinases family member, it can bind to L or K cyclins, regulates the alternative splicing and interact with HIV Tat protein, acting as a possible restriction factor, its overexpression decreases the production of some viral proteins, and suppresses the virus production. The DNA corresponding to CDK13 is replicated in cancer cells, mainly of hepatic and colon rectal types; therefore it is a target for inhibitors for cancer therapy. In order to contribute for the studies of this protein, the goal of the project is to express it using methods of recombinant DNA technology. The DNA sequence corresponding to CDK13 was amplified by polymerase chain reaction, after its purification, it was inserted to pCR-Blunt vector and cloned into E. coli DH5α competent cells. However, the DNA wasn\'t released by the BamHI and NdeI restriction enzymes. The Rosetta(DE3) cells transformed with a synthetic plasmid pET28a::CDK13 and grown in auto-induction media expressed the CDK13. After cell lysis and purification by Ni2+ affinity colum, the protein was identified by Western Blot. However, the Rosetta(DE3) cells transformed with the modified synthetic plasmid (that comprehends the DNA region which expresses the binding pocket region) induced in LB media, expressed the CDK13. Yet, it wasn\'t possible to purify the protein in the Ni2+ affinity column.
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Krämer, Thomas. "Gastrointestinale Stromatumoren (GIST) : CD117-Expression und klinischer Verlauf /." Würzburg, 2007. http://opac.nebis.ch/cgi-bin/showAbstract.pl?sys=000253020.

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Dixon-Clarke, Sarah. "Structure and inhibition of novel cyclin-dependent kinases." Thesis, University of Oxford, 2015. https://ora.ox.ac.uk/objects/uuid:3c6955c9-469a-4f4b-9577-309ccb57b742.

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Protein phosphorylation by members of the cyclin-dependent kinase (CDK) family determines the cell cycle and regulates gene transcription. CDK12 and CDK16 are relatively poorly characterised family members containing atypical domain extensions and represent novel targets for structural studies, as well as cancer drug discovery. In this thesis, I developed protocols to express and purify the human CDK12 kinase domain in complex with its obligate partner, CycK. I solved three distinct crystal structures of the complex providing insights into the structural mechanisms determining CycK assembly and kinase activation. These structures revealed a C-terminal kinase extension that folded flexibly across the active site of CDK12 to potentially gate the binding of the substrate ATP. My structures also identified Cys1039 in the C-terminal extension as the binding site for the first selective covalent inhibitor of CDK12, which has enormous potential as a pharmacological probe to investigate the functions of CDK12 in the DNA damage response and cancer. I also identified rebastinib and dabrafenib as potent, clinically-relevant inhibitors of CDK16 and solved a co-crystal structure that defined the extended type II binding mode of rebastinib. Preliminary trials using these relatively non-selective compounds to inhibit CDK16 in melanoma and medulloblastoma cancer cell lines revealed rebastinib as the more efficacious drug causing loss of cell proliferation in the 1-2 micromolar range. Use of the co-crystal structure to design more selective derivatives would be advantageous to further explore the specific role of CDK16. Finally, I identified a D-type viral cyclin from Kaposi's sarcoma-associated herpesvirus that could bind to the CDK16 kinase domain and interfere with its functional complex with human CycY causing loss of CDK16 activity. These studies provide novel insights into the structural and regulatory mechanisms of two underexplored CDK family subgroups and establish new opportunities for cancer drug development.
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Bondke, Alexander. "Design and synthesis of selective CDK7 inhibitors." Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/43965.

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Cyclin-dependent protein kinases (CDKs) have a central role in the regulation of cell proliferation, apoptosis and gene expression. CDK7, in particular, not only regulates the activation of the cell cycle kinases CDK1, CDK2, CDK4 and CDK6, but is also involved in the regulation of transcription as part of the transcription factor TFIIH-complex. While a common feature of cancer is the over-expression of cyclin, there is compelling evidence that CDK2, CDK4 and CDK6 are not essential for the cell cycle, making CDK7 a highly attractive target for anti-cancer drug development. The two pyrazolo[1,5-a]pyrimidine kinase inhibitors BS181 and BS194 were chosen as starting points for the development of a CDK7 selective drug candidate. BS181 is a selective CDK7 inhibitor (IC50: 21 nM) that shows moderate growth inhibition in the MCF7 breast cancer cell line (GI50: 15 μM) as well as in the HCT116 colorectal carcinoma cell line (GI50: 16 μM). The compound suffers from an insufficient oral bioavailability and a poor pharmacokinetic profile. The biological data of the second lead compound BS194 are significantly different: it is a CDK2 pan-inhibitor (IC50: 3 nM) with excellent growth inhibition in MCF7 (GI50: 0.12 μM) and in HCT116 cancer cells (GI50: 0.12 μM). The compound is highly bioavailable and has a good PK profile. The properties of BS181 and BS194 needed to be 'merged' to create a CDK7 selective compound with good overall properties. The multidimensional optimisation of both compounds was driven by iterative circles of computer-aided drug design (CADD), synthesis and biological assessment. Thus, analogues with highly functionalised northern, southern and eastern side chains as well as a novel series of 2,4-diaminopyrimidine kinase inhibitors were designed and subsequently synthesised.
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Kamkar, Fatemeh. "Pftaire1 (Cyclin Dependent Kinase14): Role and Function in Axonal Outgrowth During the development of the CNS." Thesis, Université d'Ottawa / University of Ottawa, 2015. http://hdl.handle.net/10393/32860.

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Cyclin Dependent Kinase (Cdk) family members play a role in CNS development. Cyclin Dependent Kinase 5 (Cdk5) is well known for its fundamental role in neuronal development and axogenesis, as well as, cell death. Other Cdks include Pctaire and Pftaire. Inhibition of Pctaire results in increased axon outgrowth, however, the role and function of Pftaire is unknown. Pftaire1 is a novel member of the Cdk family that was initially detected in a screen for cdc2-like kinases. Unpublished data from our lab reveals that Pftaire1 (Eip63E) deficiency in Drosophila melanogaster results in defects in the axon and neuronal structure of the ventral nerve cord (VNC). In mammals, Pftaire1 is highly, expressed in the CNS. Here, we proposed that Pftaire1 might have a role in axon outgrowth. To investigate the role of Pftaire1 in mammals, the first germline Pftaire1 knockout mice were generated. Considering the severe effects of Eip63E deficiency in Drosophila and the homology between mammalian and fly Pftaire1, CNS defects in the mouse were anticipated. However, to date, no gross abnormalities have been detected in the overall morphology, fertility, life span, or anatomical brain structures of the Pftaire1 deficient mice. This may be due to the presence of other post-mitotic Cdk proteins that are highly similar to Pftaire1. For instance, mammals possess Pftaire (1, and 2), as well as, Pctaire (1, 2, and 3), while Drosophila only possess the Pftaire1 orthologue where the Pftaire2 and Pctaire (1, 2, and 3) are absent. Furthermore, the mice were of mixed background. In spite of this, we demonstrated that Pftaire1 deficient neurons showed increased axon length, in the initial phases of culture. This was confirmed by expression of dominant negative (DN) D228N-Pftaire1 in wild type neurons. Also classification of axons into different ranges, reveals a higher percentage of hyperextended neurites in D228N and Pftaire1 knockout mice. The mechanism by which Pftaire1 controls axon outgrowth is unknown. In this study we show that, Pftaire1 interacts physically with the small GTPase proteins Rac1, Cdc42, and RhoA. Importantly, we showed that Pftaire1 phosphorylates GDP-RhoA on a serine residue. We propose that this regulates RhoA activity, which in turn controls axon outgrowth.
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Dubbury, Sara Jane. "Cdk12 regulates DNA repair Genes by suppressing intronic polyadenylation." Thesis, Massachusetts Institute of Technology, 2018. http://hdl.handle.net/1721.1/115596.

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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2018.
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis. Vita.
Includes bibliographical references.
During transcription, cyclin-dependent kinases (CDKs) dynamically phosphorylate the C-terminal domain (CTD) of RNA Polymerase II (RNAPII) to recruit factors that coordinate transcription and mRNA biogenesis. Cdk12 phosphorylates Serine 2 (Ser2) of the RNAPII CTD, a modification associated with the regulation of transcription elongation, splicing, and cleavage/polyadenylation. Unlike other transcriptional CDKs that regulate most expressed genes, Cdk12 depletion abrogates the expression of homologous recombination (HR) genes relatively specifically, suppressing the HR DNA damage repair pathway and sensitizing cells to genotoxic stresses that cause replication fork collapse, such as Parp1 inhibitors. The proposed role for Cdk12 in regulating HR is clinically significant for two reasons. First, Cdk12 loss-of-function mutations populate high-grade serous ovarian carcinoma and castration-resistant prostate tumors raising the possibility that Cdk12 mutational status may predict the effectiveness of chemotherapeutics that target HR-deficient tumors. Second, readily available small molecule inhibitors of Cdk12 induce sensitization of HR-competent tumors to Parp1 inhibitors in vivo raising the possibility that inhibitors against Cdk12 could be used as chemotherapeutics. Despite this growing clinical interest, the mechanism behind Cdk12's regulation of HR genes remains unknown. Here we show that Cdk12 suppresses intronic polyadenylation (IPA) and that this mechanism explains the exquisite sensitivity of HR genes to Cdk12 loss. We find that Cdk12 globally enhances transcription elongation rate to kinetically suppress IPA events. Many HR genes harbor multiple IPA sites per gene, and the cumulative effect of these sites accounts for the increased sensitivity of HR genes to Cdk12. Finally, we find evidence that Cdk12 LOF mutations and deletions cause upregulation of IPA sites in HR genes in human tumors. Our results define the mechanism by which Cdk12 regulates transcription, mRNA biogenesis, and the HR pathway. This work clarifies the biological function of CDK12 and underscores its potential both as a chemotherapeutic target and as a tumor biomarker.
by Sara Jane Dubbury.
Ph. D.
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Maino, Marcelo Marafon. "Expressão imunoistoquímica de CD117 no carcinoma epidermóide de esôfago." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2008. http://hdl.handle.net/10183/53132.

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Objetivo: Investigar a expressão imunoistoquímica de CD117 em um grupo de pacientes com carcinoma epidermóide de esôfago Pacientes e Métodos: Vinte e sete pacientes com carcinoma epidermóide de esôfago submetidos à ressecção cirúrgica no Hospital de Clínicas de Porto Alegre da Universidade Federal do Rio Grande do Sul foram avaliados para imunoreatividade do CD117. Como grupo controle, foram utilizadas biópsias de mucosa esofágica de dez indivíduos saudáveis. A avaliação imunoistoquímica dos tecidos foi realizada com anticorpo monoclonal anti-CD117 (DAKO). Resultados: Foram avaliados 21 (78%) homens e 6 (12%) mulheres com idade média de 58 anos (36 a 77). A maioria dos pacientes apresentava estadiamento TNM IIb ou III, e a sobrevida média foi de 21 meses (2 a 72). A reação imunoistoquímica em membrana produzida pelo anticorpo anti-CD117 foi considerada positiva em 4 dos 27 dos casos analisados (15%) . Conclusões: Esses achados sugerem que CD117 deve ser investigado como marcador para o carcinoma epidermóide de esôfago. Estudos adicionais são necessários em outras amostras populacionais, para melhor definir o papel do CD117 nesses tumores.
Aim: To investigate the CD117 expression in specimens of patients with squamous cell carcinoma of the esophagus (SCCE). Methods: A pilot study was performed for CD177 immunoreactivity, using a monoclonal antibody against CD117 (DAKO), on 27 esophageal squamous cell carcinoma specimens from patients who underwent surgical resection at the Hospital de Clínicas de Porto Alegre University Hospital, Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. As a control group, specimens of esophageal mucosa obtained from 10 healthy subjects were also studied. Results: Twenty-one (78%) males and six (12%) females with median (sd) age of 58 (8) years, ranging from 36 to 77 years. Most of the patients were of TNM stage IIb or III and mean overall survival was 21 (2 to 72) months. Cytoplasmic membrane CD117 immunoreactivity was demonstrated in only 4 (15%) out of 27 tumors and in none of the controls (0%). Conclusions: These results suggest that the decreased expression of CD117 may be due to lack of control of the cell cycle in SCCE. Additional studies are needed to better define the role of the CD117 in such tumors.
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Books on the topic "CDK17"

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Mackiewicz, Monika. Die tumorartige Proliferation Theileria-infizierter Rinderleukozyten: Zellzyklusabhängige Phosphorylierung des Theileria annulata Surface Protein (TaSP) durch die bovine Cyclin-Dependent Kinase 1 (CDK1). 2013.

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Neville, John. CCNB1, CCNB2, CCNA1, CCNA2, SYT1, SYT2, CKS2, CKS1B, CCNB3, SKP1, CDK1, RPS23, RPS27A, ZFAND4, RPS27, RPS27l, BUB1, BUB1B Could Play Significant Roles in the Aetiology of Schizophrenia by Acting As Points of Contact Between ALDH18A1 and SEC23IP (COP2). Lulu Press, Inc., 2017.

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Book chapters on the topic "CDK17"

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Hu, Dongli, and Jill M. Lahti. "CDK11." In Encyclopedia of Signaling Molecules, 995–1002. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-67199-4_546.

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Hu, Dongli, and Jill M. Lahti. "CDK11." In Encyclopedia of Signaling Molecules, 1–8. New York, NY: Springer New York, 2016. http://dx.doi.org/10.1007/978-1-4614-6438-9_546-1.

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van Roy, Frans, Volker Nimmrich, Anton Bespalov, Achim Möller, Hiromitsu Hara, Jacob P. Turowec, Nicole A. St. Denis, et al. "CDK11." In Encyclopedia of Signaling Molecules, 373–79. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4419-0461-4_546.

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Mir, Manzoor Ahmad, and Burhan Ul Haq. "CDK1 Dysregulation in Breast Cancer." In Therapeutic potential of Cell Cycle Kinases in Breast Cancer, 195–210. Singapore: Springer Nature Singapore, 2023. http://dx.doi.org/10.1007/978-981-19-8911-7_9.

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Shuttleworth, John. "The regulation and functions of cdk7." In Progress in Cell Cycle Research, 229–40. Boston, MA: Springer US, 1995. http://dx.doi.org/10.1007/978-1-4615-1809-9_18.

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Lopes, José Manuel. "C-Kit (CD117), Gastrointestinal Stromal Tumors (GISTs)." In Encyclopedia of Pathology, 137–40. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-40560-5_1572.

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Salaun, Patrick, Yoann Rannou, and Prigent Claude. "Cdk1, Plks, Auroras, and Neks: The Mitotic Bodyguards." In Hormonal Carcinogenesis V, 41–56. New York, NY: Springer New York, 2008. http://dx.doi.org/10.1007/978-0-387-69080-3_4.

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Pinhero, Reena, and Krassimir Yankulov. "Expression and Purification of Recombinant CDKs: CDK7, CDK8, and CDK9." In Methods in Molecular Biology, 13–28. New York, NY: Springer New York, 2016. http://dx.doi.org/10.1007/978-1-4939-2926-9_3.

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Rodríguez-Gabriel, Miguel A. "Analyzing Cdc2/Cdk1 Activation During Stress Response in Schizosaccharomyces pombe." In Methods in Molecular Biology, 383–92. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-0888-2_20.

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Dumitru, Ana Maria G., and Duane A. Compton. "Identifying Cyclin A/Cdk1 Substrates in Mitosis in Human Cells." In Methods in Molecular Biology, 175–82. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-1904-9_13.

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Conference papers on the topic "CDK17"

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Bradley, Michael, Jason Marineau, Yoon Choi, Kristin Hamman, Goran Malojcic, David Orlando, Yixuan Ren, et al. "Abstract 1143: Targeting the transcriptional kinases CDK12 and CDK13 in breast and ovarian cancer." In Proceedings: AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7445.am2017-1143.

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Денисова, Дарья Андреевна. "CYCLIN-DEPENDENT KINASES CDK8 / 19 AND THEIR INFLUENCE ON THE ORIGIN AND DEVELOPMENT OF TUMOR PROCESSES." In Наука. Исследования. Практика: сборник избранных статей по материалам Международной научной конференции (Санкт-Петербург, Апрель 2020). Crossref, 2020. http://dx.doi.org/10.37539/srp290.2020.80.21.015.

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Циклин-зависимая киназа CDK8 и её паралог, CDK19, являются ферментами, задействованными в развитии таких онкологических заболеваний, как рак молочной железы, колоректальный рак, рак простаты, острый миелоидный лейкоз и другие. The cyclin-dependent kinase CDK8 and its paralogue, CDK19, are enzymes involved in the development of oncological diseases such as breast cancer, colorectal cancer, prostate cancer, acute myeloid leukemia and others.
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Hovdar, L., J. Rössler, P. Hechenberger, S. Rainer, K. Ausserlechner, B. Greiderer-Kleinlercher, M. Ausserlechner, C. Marth, AG Zeimet, and H. Fiegl. "Effekte einer CDK12/13 Inhibition beim Ovarialkarzinom." In Kongressabstracts zur Gemeinsamen Jahrestagung der Österreichischen Gesellschaft für Gynäkologie und Geburtshilfe (OEGGG) und der Bayerischen Gesellschaft für Geburtshilfe und Frauenheilkunde e.V. (BGGF). Georg Thieme Verlag KG, 2021. http://dx.doi.org/10.1055/s-0041-1730504.

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Kerr, Bethany. "Abstract 2229: CD117 expression and activation in prostate cancer progression." In Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.am2015-2229.

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Harris, Koran, Lihong Shi, Taylor Peak, Stephanie Sanders, Aleksander Skardal, and Bethany Kerr. "Abstract 1983: CD117 expression and activation induce prostate cancer metastasis." In Proceedings: AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7445.am2017-1983.

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Fernandes, Vanessa C., Thales C. Nepomuceno, Renato S. Carvalho, Guilherme Suarez-Kurtz, Alvaro N. Monteiro, and Marcelo A. Carvalho. "Abstract A04: Structural and functional caracterization of BARD1/CDK13 interaction." In Abstracts: AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1557-3265.tcm17-a04.

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Shi, Lihong, Brittni Foster, Koran Harris, Aleksander Skardal, and Bethany A. Kerr. "Abstract B027: CD117 tyrosine kinase activation drives prostate cancer aggressiveness." In Abstracts: AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; December 2-5, 2017; Orlando, Florida. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1538-7445.prca2017-b027.

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Garcia-Martinez, Juan Manuel, Andreas Wernitznig, Joerg Rinnenthal, Maria Antonietta Impagnatiello, Frank Hilberg, Craig Giragossian, Norbert Kraut, Mark Pearson, and Klaus-Peter Kuenkele. "Abstract 2051: BI 905711, a novel CDH17-targeting TRAILR2 agonist, effectively triggers tumor cell apoptosis and tumor regressions selectively in CDH17-positive colorectal cancer models." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.sabcs18-2051.

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Garcia-Martinez, Juan Manuel, Andreas Wernitznig, Joerg Rinnenthal, Maria Antonietta Impagnatiello, Frank Hilberg, Craig Giragossian, Norbert Kraut, Mark Pearson, and Klaus-Peter Kuenkele. "Abstract 2051: BI 905711, a novel CDH17-targeting TRAILR2 agonist, effectively triggers tumor cell apoptosis and tumor regressions selectively in CDH17-positive colorectal cancer models." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.am2019-2051.

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Chilà, R., N. Panini, F. Guffanti, and G. Damia. "PO-040 Characterisation of CDK12 knocked out ovarian cancer cell lines." In Abstracts of the 25th Biennial Congress of the European Association for Cancer Research, Amsterdam, The Netherlands, 30 June – 3 July 2018. BMJ Publishing Group Ltd, 2018. http://dx.doi.org/10.1136/esmoopen-2018-eacr25.85.

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