The family of cyclin-dependent kinases (Cdks) consists of 21 proteins whose activities usually require association with a specific cyclin subunit [1]. The first Cdks to be described were regulators of the cell cycle, such as Cdk1, Cdk2, Cdk4, and Cdk6. Their corresponding cyclins are also...
目前,仍然缺乏对小分子抑制动态相互作用分子机制进行高通量表征的方法,极大限制了CDK12/CDK13抑制剂的理性设计和相关药物研发。 在本工作中,合作团队发展了整合LRP-MS和nMS的结构质谱策略,系统研究了多种小分子抑制剂调控下CDK12/CDK13-Cyclin K复合物的动态构象变化和整体蛋白组装。合作团队通过前期发展的LRP-MS策略...
16. Kohoutek J, Blazek D: Cyclin K goes with Cdk12 and Cdk13. Cell Div 2012, 7:12. 17. Guo Z, Stiller JW: Comparative genomics of cyclin-dependent kinases suggest co-evolution of the RNAP II C-terminal domain and CTD-directed CDKs. BMC Genomics 2004, 5:69. 18. Echalier A, ...
CDK12 and CDK13 regulate gene expression through translation and splicing of mRNA. Impaired activity of CDK12 has been shown to reduce the expression of a range of genes involved in DNA homologous repair leading to the induction of a 'BRCAness' phenotype in cells. CDK12 inhibitors have the ...
Such canonical, cell cycle-associated functions are driven by a small subset of the known mammalian CDKs (CDK1, CDK2, CDK3, CDK4, and CDK6), and their associated cyclin partners (A-, B-, D-, and E- type) – here referred to simply as cell cycle associated CDK/cyclin complexes. ...
Despite the large number of CDKs and cyclins, only a few have been strongly implicated in breast cancer pathogenesis. This review focuses primarily on CDK4 and CDK6, which have largely overlapping though not entirely identical specificity, as well as cyclin D1, the most characterized member of...
The cell cycle and apoptosis were assessed to study the role of LAIR1 in the growth of glioma cells. PI staining demonstrated that LAIR1 knockdown did cause G1 phase cell cycle arrest (Fig.3E). Additionally, compared to vector cells, the CDK4/6 inhibitor palbociclib demonstrated lower sensiti...
MiR-188 inhibits both mRNA and protein expression of CCND1, CCND3, CCNE1, CCNA2, CDK4 and CDK2, suppresses Rb phosphorylation and downregulates E2F transcriptional activity. The expression level of miR-188 also inversely correlates with the expression of miR-188 targets in human nasopharyngeal ...
Given their critical roles as transcription factors capable of controlling cellular proliferation and differentiation during embryogenesis, there has been increasing interest in the possible role of homeobox genes as potential proto-oncogenes when their regulation goes awry. One such well-documented instance...
Liang K, Gao X, Gilmore JM, Florens L, Washburn MP, Smith E, Shilatifard A (2015) Characterization of human cyclin-dependent kinase 12 (CDK12) and CDK13 complexes in C-terminal domain phosphorylation, gene transcription, and RNA processing. Mol Cell Biol 35: 928 - 938...