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Gene Review

CDK7  -  cyclin-dependent kinase 7

Homo sapiens

Synonyms: 39 kDa protein kinase, CAK, CAK1, CDK-activating kinase 1, CDKN7, ...
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Disease relevance of CDK7


High impact information on CDK7


Chemical compound and disease context of CDK7

  • Activity of thymidine kinase 1 in serum (STK) is a useful marker for leukaemia and lymphoma, but not for solid tumors [9].

Biological context of CDK7


Anatomical context of CDK7

  • The human MAT1 gene expresses a single 1.6-kb transcript, the steady-state level of which, like CDK7 and cyclin H, varies significantly in different cell lines and in different terminally differentiated tissues [15].
  • CDK7, a member of the cyclin-dependent protein kinase family, regulates the activities of other CDKs through phosphorylation on their activation segment and hence contributes to control of the eukaryotic cell cycle [16].
  • Here, we analyze CAK activities in HeLa cells using cdk2-affinity chromatography [17].
  • Protein kinase C inhibits the CAK-CDK2 cyclin-dependent kinase cascade and G1/S cell cycle progression in human diploid fibroblasts [18].
  • Here we report the colocalization of CDK7 and the phosphorylated form of CTD (phosphoCTD) to actively transcribing genes in intact salivary gland cells of Chironomus tentans [19].

Associations of CDK7 with chemical compounds

  • Analysis of preinitiation complexes formed in immunodepleted extracts suggests that CDK9 phosphorylates serine 2, while CDK7 phosphorylates serine 5 [20].
  • Apart from the main cell cycle-regulating kinase CDK2, olomoucine II exerts specificity for CDK7 and CDK9, with important functions in the regulation of RNA transcription [21].
  • Addition of GW9662, which is a PPARgamma specific antagonist, could reserve the modulation action on CDK7 [22].
  • CONCLUSION: Our results support the hypothesis that cell cycle arrest induced by C2-ceramide may be mediated via accumulation of p21 and reduction of cyclinD1 and CDK7, at least partly, through PPARgamma activation [22].
  • In addition, resveratrol-treated cells were shown to have a low level of CDK7 kinase-Thr(161)-phosphorylated p34(CDC2) [23].

Physical interactions of CDK7

  • Isolation and characterization of two human transcription factor IIH (TFIIH)-related complexes: ERCC2/CAK and TFIIH [24].
  • Little is known about the regulation of the CAK complex through cyclin H. In this study we further analyzed cyclin H regulation and identified two basic clusters in the C terminus of the protein as putative nuclear localization sequences (NLSs) [25].
  • In addition, other substrates of the CAK complex have been identified when CAK is assembled with the TFIIH core proteins, thereby regulating transcription and nucleotide excision repair [25].
  • An analysis of cyclin-dependent kinase complex regulators revealed increased expression of p27(KIP1) and decreased expression of Cdk7 in c-myc-/- cells [26].
  • We next tested whether p21 could bind to Cdk7, a component of the cyclin-activating kinase complex [27].

Enzymatic interactions of CDK7

  • In addition, GA-treated cells were shown to have a low level of CDK7 kinase-phosphorylated-Thr(161) CDC2/p34 (active) [12].
  • p53 is phosphorylated by CDK7-cyclin H in a p36MAT1-dependent manner [28].
  • We report that serum stimulation causes a gradual, sustained increase in the activity of CDK-activating kinase (CAK) that phosphorylates CDK2 at Thr160, which starts by 5 h after serum stimulation and reaches the maximal plateau level at around the G1/S boundary [18].
  • We present evidence that in neuroblastoma CHP126 cells, CAK interacts with and phosphorylates retinoblastoma tumor suppressor protein (pRb) and retinoid X receptor alpha (RXRalpha) [29].
  • We report here that CAK binds to and phosphorylates PML/RARalpha in actively proliferating APL cells [30].

Regulatory relationships of CDK7

  • The cyclin-dependent kinase (CDK)-activating kinase (CAK) phosphorylates a conserved threonine residue on CDKs and activates them [31].
  • When R2 was expressed in budding yeast CAK mutant, the suppression activity in terms of temperature-sensitivity was enhanced by co-expression with Os;cycH;1 [32].
  • Circumstantial evidence obtained in our studies and by other investigators suggests that STSP-induced arrest may be due to the inhibition of cdk-activating kinase [33].
  • Cdk2 is activated in the nucleus by Cdk-activating kinase through Thr160 phosphorylation and by cdc25A phosphatase via Thr14 and Tyr15 dephosphorylation [34].
  • Specific inhibition of p40MO15 synthesis in stage VI oocytes by antisense oligonucleotide depletion of MO15 mRNA increases the rate of progesterone induced H1 kinase activation and oocyte maturation [35].

Other interactions of CDK7

  • Three-dimensional structure of human cyclin H, a positive regulator of the CDK-activating kinase [36].
  • This TFIIH*-dependent transcription reaction was stimulated by ERCC2/CAK [24].
  • CDK2-7, moreover, phosphorylated wild-type CDK7 but not CDK2 [11].
  • In contrast, neither CDK4 nor CDK7 itself can phosphorylate the CDK7 T loop in vitro [11].
  • Although PNQALRE/CCRK was recently proposed to activate Cdk2, we show that the monomeric protein has no intrinsic CAK activity [37].

Analytical, diagnostic and therapeutic context of CDK7


  1. HIV-1 Tat-associated RNA polymerase C-terminal domain kinase, CDK2, phosphorylates CDK7 and stimulates Tat-mediated transcription. Nekhai, S., Zhou, M., Fernandez, A., Lane, W.S., Lamb, N.J., Brady, J., Kumar, A. Biochem. J. (2002) [Pubmed]
  2. Cyclin-dependent kinase activating kinase/Cdk7 co-localizes with PKC-iota in human glioma cells. Bicaku, E., Patel, R., Acevedo-Duncan, M. Tissue & cell. (2005) [Pubmed]
  3. Two novel human serine/threonine kinases with homologies to the cell cycle regulating Xenopus MO15, and NIMA kinases: cloning and characterization of their expression pattern. Levedakou, E.N., He, M., Baptist, E.W., Craven, R.J., Cance, W.G., Welcsh, P.L., Simmons, A., Naylor, S.L., Leach, R.J., Lewis, T.B. Oncogene (1994) [Pubmed]
  4. XPD mutations prevent TFIIH-dependent transactivation by nuclear receptors and phosphorylation of RARalpha. Keriel, A., Stary, A., Sarasin, A., Rochette-Egly, C., Egly, J.M. Cell (2002) [Pubmed]
  5. Stimulation of RAR alpha activation function AF-1 through binding to the general transcription factor TFIIH and phosphorylation by CDK7. Rochette-Egly, C., Adam, S., Rossignol, M., Egly, J.M., Chambon, P. Cell (1997) [Pubmed]
  6. The Cdk-activating kinase (CAK) from budding yeast. Kaldis, P., Sutton, A., Solomon, M.J. Cell (1996) [Pubmed]
  7. A novel cyclin associates with MO15/CDK7 to form the CDK-activating kinase. Fisher, R.P., Morgan, D.O. Cell (1994) [Pubmed]
  8. The MO15 cell cycle kinase is associated with the TFIIH transcription-DNA repair factor. Roy, R., Adamczewski, J.P., Seroz, T., Vermeulen, W., Tassan, J.P., Schaeffer, L., Nigg, E.A., Hoeijmakers, J.H., Egly, J.M. Cell (1994) [Pubmed]
  9. Concentration of thymidine kinase 1 in serum (S-TK1) is a more sensitive proliferation marker in human solid tumors than its activity. He, Q., Zhang, P., Zou, L., Li, H., Wang, X., Zhou, S., Fornander, T., Skog, S. Oncol. Rep. (2005) [Pubmed]
  10. Regulation of CDK7 substrate specificity by MAT1 and TFIIH. Yankulov, K.Y., Bentley, D.L. EMBO J. (1997) [Pubmed]
  11. Reciprocal activation by cyclin-dependent kinases 2 and 7 is directed by substrate specificity determinants outside the T loop. Garrett, S., Barton, W.A., Knights, R., Jin, P., Morgan, D.O., Fisher, R.P. Mol. Cell. Biol. (2001) [Pubmed]
  12. Gambogic acid-induced G2/M phase cell-cycle arrest via disturbing CDK7-mediated phosphorylation of CDC2/p34 in human gastric carcinoma BGC-823 cells. Yu, J., Guo, Q.L., You, Q.D., Zhao, L., Gu, H.Y., Yang, Y., Zhang, H.W., Tan, Z., Wang, X. Carcinogenesis (2007) [Pubmed]
  13. A cyclin associated with the CDK-activating kinase MO15. Mäkelä, T.P., Tassan, J.P., Nigg, E.A., Frutiger, S., Hughes, G.J., Weinberg, R.A. Nature (1994) [Pubmed]
  14. Requirements for cdk7 in the assembly of cdk1/cyclin B and activation of cdk2 revealed by chemical genetics in human cells. Larochelle, S., Merrick, K.A., Terret, M.E., Wohlbold, L., Barboza, N.M., Zhang, C., Shokat, K.M., Jallepalli, P.V., Fisher, R.P. Mol. Cell (2007) [Pubmed]
  15. Molecular cloning of CDK7-associated human MAT1, a cyclin-dependent kinase-activating kinase (CAK) assembly factor. Yee, A., Nichols, M.A., Wu, L., Hall, F.L., Kobayashi, R., Xiong, Y. Cancer Res. (1995) [Pubmed]
  16. The crystal structure of human CDK7 and its protein recognition properties. Lolli, G., Lowe, E.D., Brown, N.R., Johnson, L.N. Structure (Camb.) (2004) [Pubmed]
  17. Analysis of CAK activities from human cells. Kaldis, P., Solomon, M.J. Eur. J. Biochem. (2000) [Pubmed]
  18. Protein kinase C inhibits the CAK-CDK2 cyclin-dependent kinase cascade and G1/S cell cycle progression in human diploid fibroblasts. Hamada, K., Takuwa, N., Zhou, W., Kumada, M., Takuwa, Y. Biochim. Biophys. Acta (1996) [Pubmed]
  19. Heat-shock-specific phosphorylation and transcriptional activity of RNA polymerase II. Egyházi, E., Ossoinak, A., Lee, J.M., Greenleaf, A.L., Mäkelä, T.P., Pigon, A. Exp. Cell Res. (1998) [Pubmed]
  20. Tat modifies the activity of CDK9 to phosphorylate serine 5 of the RNA polymerase II carboxyl-terminal domain during human immunodeficiency virus type 1 transcription. Zhou, M., Halanski, M.A., Radonovich, M.F., Kashanchi, F., Peng, J., Price, D.H., Brady, J.N. Mol. Cell. Biol. (2000) [Pubmed]
  21. Antiproliferative activity of olomoucine II, a novel 2,6,9-trisubstituted purine cyclin-dependent kinase inhibitor. Krystof, V., McNae, I.W., Walkinshaw, M.D., Fischer, P.M., Müller, P., Vojtesek, B., Orság, M., Havlícek, L., Strnad, M. Cell. Mol. Life Sci. (2005) [Pubmed]
  22. Mechanisms involved in ceramide-induced cell cycle arrest in human hepatocarcinoma cells. Wang, J., Lv, X.W., Shi, J.P., Hu, X.S. World J. Gastroenterol. (2007) [Pubmed]
  23. Resveratrol-induced G2 arrest through the inhibition of CDK7 and p34CDC2 kinases in colon carcinoma HT29 cells. Liang, Y.C., Tsai, S.H., Chen, L., Lin-Shiau, S.Y., Lin, J.K. Biochem. Pharmacol. (2003) [Pubmed]
  24. Isolation and characterization of two human transcription factor IIH (TFIIH)-related complexes: ERCC2/CAK and TFIIH. Reardon, J.T., Ge, H., Gibbs, E., Sancar, A., Hurwitz, J., Pan, Z.Q. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  25. Cyclin H is targeted to the nucleus by C-terminal nuclear localization sequences. Krempler, A., Kartarius, S., Günther, J., Montenarh, M. Cell. Mol. Life Sci. (2005) [Pubmed]
  26. c-Myc regulates cyclin D-Cdk4 and -Cdk6 activity but affects cell cycle progression at multiple independent points. Mateyak, M.K., Obaya, A.J., Sedivy, J.M. Mol. Cell. Biol. (1999) [Pubmed]
  27. The amino terminus of Cdk2 binds p21. Moskowitz, N.K., Borao, F.J., Dardashti, O., Cohen, H.D., Germino, F.J. Oncol. Res. (1996) [Pubmed]
  28. p53 is phosphorylated by CDK7-cyclin H in a p36MAT1-dependent manner. Ko, L.J., Shieh, S.Y., Chen, X., Jayaraman, L., Tamai, K., Taya, Y., Prives, C., Pan, Z.Q. Mol. Cell. Biol. (1997) [Pubmed]
  29. MAT1-modulated cyclin-dependent kinase-activating kinase activity cross-regulates neuroblastoma cell G1 arrest and neurite outgrowth. Zhang, S., He, Q., Peng, H., Tedeschi-Blok, N., Triche, T.J., Wu, L. Cancer Res. (2004) [Pubmed]
  30. Retinoic acid induces leukemia cell G1 arrest and transition into differentiation by inhibiting cyclin-dependent kinase-activating kinase binding and phosphorylation of PML/RARalpha. Wang, J.G., Barsky, L.W., Davicioni, E., Weinberg, K.I., Triche, T.J., Zhang, X.K., Wu, L. FASEB J. (2006) [Pubmed]
  31. p42, a novel cyclin-dependent kinase-activating kinase in mammalian cells. Liu, Y., Wu, C., Galaktionov, K. J. Biol. Chem. (2004) [Pubmed]
  32. Activation of CDK-activating kinase is dependent on interaction with H-type cyclins in plants. Yamaguchi, M., Fabian, T., Sauter, M., Bhalerao, R.P., Schrader, J., Sandberg, G., Umeda, M., Uchimiya, H. Plant J. (2000) [Pubmed]
  33. CDK4/cyclin D1/PCNA complexes during staurosporine-induced G1 arrest and G0 arrest of human fibroblasts. Gadbois, D.M., Peterson, S., Bradbury, E.M., Lehnert, B.E. Exp. Cell Res. (1995) [Pubmed]
  34. Vitamin D inhibits G1 to S progression in LNCaP prostate cancer cells through p27Kip1 stabilization and Cdk2 mislocalization to the cytoplasm. Yang, E.S., Burnstein, K.L. J. Biol. Chem. (2003) [Pubmed]
  35. p40MO15, a cdc2-related protein kinase involved in negative regulation of meiotic maturation of Xenopus oocytes. Shuttleworth, J., Godfrey, R., Colman, A. EMBO J. (1990) [Pubmed]
  36. Three-dimensional structure of human cyclin H, a positive regulator of the CDK-activating kinase. Kim, K.K., Chamberlin, H.M., Morgan, D.O., Kim, S.H. Nat. Struct. Biol. (1996) [Pubmed]
  37. The cyclin-dependent kinase (CDK) family member PNQALRE/CCRK supports cell proliferation but has no intrinsic CDK-activating kinase (CAK) activity. Wohlbold, L., Larochelle, S., Liao, J.C., Livshits, G., Singer, J., Shokat, K.M., Fisher, R.P. Cell Cycle (2006) [Pubmed]
  38. Interactions of Cdk7 and Kin28 with Hint/PKCI-1 and Hnt1 histidine triad proteins. Korsisaari, N., Mäkelä, T.P. J. Biol. Chem. (2000) [Pubmed]
  39. Molecular cloning of the human CAK1 gene encoding a cyclin-dependent kinase-activating kinase. Wu, L., Yee, A., Liu, L., Carbonaro-Hall, D., Venkatesan, N., Tolo, V.T., Hall, F.L. Oncogene (1994) [Pubmed]
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