Disease relevance of Cdk7

• A variant mouse plasmacytoma (MPC)-associated translocation chromosome has arisen by pericentric inversion and exchange of the distal segments of a Robertsonian 6;15 fusion chromosome in the CAK TEPC 1198 mouse plasmacytoma, as described earlier [1].

High impact information on Cdk7

• Stabilization and activation of CAK by p36 is independent of the phosphorylation state of T170, the conserved activating residue of CDK7 [2].
• Levels of the cdk inhibitor p27Klp1 increase in cAMP-treated cells, and its immunodepletion from inhibitory lysates restores CAK-mediated cdk4 activation [3].
• The near-diploid mouse cell line CAK is heterozygous for two electrophoretic variants of ES-10 [4].
• Recessive Adk- mutants of CAK have been isolated and analyzed for Es-10 phenotype and karyotypic abnormalities [4].
• However, formation of the ternary CAK complex, CAK activity, and the CDK2 level with activating phosphorylation were inhibited by expression of the HCV core [5].

Biological context of Cdk7

• Here, we show that cyclin H and Cdk7 are present during meiosis [6].
• Assembly of active CDK7-cyclin H dimers can also occur through an alternative p36-independent pathway that requires phosphorylation of T170 by a CAK-activating kinase, or CAKAK [2].
• The deduced amino acid (aa) sequence shows 85% overall identity with the Xenopus laevis MO15 PK (the catalytic subunit of CAK) [7].
• A recent study demonstrated that LPS activated CAK without generating ceramide, suggesting that the LPS stimulation of cells mimics the second messenger function of ceramide [8].
• Laparotomy significantly impaired microbicidal activity (O2-, percent CAP, and percent CAK) and antigen presentation on postoperative day 1 [9].

Anatomical context of Cdk7

• Meiotic expression of the cyclin H/Cdk7 complex in male germ cells of the mouse [6].
• Using reverse transcription-polymerase chain reaction and in situ hybridization, we show that the mRNAs encoding cyclin H and Cdk7 are abundant in spermatocytes [6].
• The direct effect of HCV core on CAK was further assessed in the cell-free system by adding the in vitro translated HCV core protein to the anti-CDK7 immunoprecipitate from the cell [5].
• Administration of IL-4 significantly reduced the incidence of bacteria positive MLN and increased PMO superoxide production, CAP, CAK, and MLN lymphocyte mitogenesis [10].
• PMO and KC were harvested to measure tumor necrosis factor production, macrophage binding of fluorescent-labeled lipopolysaccharide, and Candida albicans phagocytosis (CAP) and killing (CAK); KC-hepatocyte interaction was assessed by hepatocyte protein synthesis [10].

Associations of Cdk7 with chemical compounds

• Oral feeding of a CDD resulted in significant impairment of mesenteric lymphocyte mixed lymphocyte response and cytotoxic T-lymphocyte functions and decreased PMO tumor necrosis factor production, fluorescent-labeled lipopolysaccharide binding, CAP, and CAK [10].

Enzymatic interactions of Cdk7

• The active Cdk7-containing enzyme also phosphorylates and activates wt Cdk5 but not mutated Cdk5(Ser159Ala) [11].

Regulatory relationships of Cdk7

• Conversely, blocked Cdk7 immunoprecipitate does not phosphorylate nor activate Cdk5 [11].

Other interactions of Cdk7

• These findings indicate that Cdk7 functions as a Cdk5 activating kinase in brain [11].
• These results suggest that cyclin D1 (T156A or T156E) forms abortive complexes with CDK4 that prevent recognition by CAK and by other cellular factors that are required for their nuclear localization [12].
• Moreover, we provide evidence indicating that MAP kinases control Cdk2 Thr-160 activating phosphorylation and function, possibly by regulating the activity of a Cdk-activating kinase, thus promoting the re-initiation of DNA synthesis [13].

References