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Gene Review

Cdk1  -  cyclin-dependent kinase 1

Rattus norvegicus

Synonyms: CDK1, Cdc2, Cdc2a, Cdkn1, Cell division control protein 2 homolog, ...
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Disease relevance of Cdc2a


High impact information on Cdc2a

  • Vertebrate eggs are arrested at metaphase of meiosis II with stable cyclin B and high cyclin B/Cdc2 kinase activity [6].
  • Although p21, an inhibitor of cyclin-dependent kinase (Cdk) that is induced by DNA damage may partly account for the arrest in G1 (ref. 1), the mechanism is little understood [7].
  • Here we show that when a constitutively active mutant of calmodulin-dependent protein kinase II (CaM KII) is added to a CSF extract, cyclin degradation and Cdc2 kinase inactivation occur even in the absence of Ca2+, and the extract loses its ability to cause metaphase arrest when transferred into embryos [8].
  • Finally, the direct microinjection of constitutively active CaM KII into unfertilized eggs inactivates Cdc2 kinase and CSF, even in the absence of a Ca2+ transient [8].
  • Expression of dominant-negative mutants of cdk5 (cdk5N144 and cdk5T33) inhibited neurite outgrowth, which was rescued by coexpression of the wild-type proteins [9].

Chemical compound and disease context of Cdc2a


Biological context of Cdc2a


Anatomical context of Cdc2a


Associations of Cdc2a with chemical compounds


Physical interactions of Cdc2a


Regulatory relationships of Cdc2a


Other interactions of Cdc2a


Analytical, diagnostic and therapeutic context of Cdc2a

  • To characterize this growth arrest, we examined the activity of cyclin-dependent kinase (Cdk) 2 in unexposed liver and in AAF-exposed liver after growth induction by partial hepatectomy (PH) [38].
  • The cell cycle regulatory enzyme, cdk (cyclin-dependent kinase) 2 kinase, is activated in the rat carotid artery after balloon angioplasty injury, and may mediate smooth muscle proliferation [39].
  • We determined whether CDK activation occurs in mature adult neurons during focal stroke in vivo and whether this signal was required for neuronal death after reperfusion injury [40].
  • Western blot analysis showed that the amount of Cdc2 increased when either rat kidney fibroblasscr2 or scr3 was introduced into the cdc2-L7 and cdc13-117 mutant cells of S.pombe [41].
  • Immunohistochemistry of formalin-fixed liver demonstrated a cytosolic localization of immunoreactive CDK1 and nuclear localization of immunoreactive PCNA in proliferating cells of WY14,643-treated rat livers [42].


  1. Hepatobiliary damage and changes in hepatic gene expression caused by the antitumor drug ecteinascidin-743 (ET-743) in the female rat. Donald, S., Verschoyle, R.D., Edwards, R., Judah, D.J., Davies, R., Riley, J., Dinsdale, D., Lopez Lazaro, L., Smith, A.G., Gant, T.W., Greaves, P., Gescher, A.J. Cancer Res. (2002) [Pubmed]
  2. Glucocorticoids stimulate p21 gene expression by targeting multiple transcriptional elements within a steroid responsive region of the p21waf1/cip1 promoter in rat hepatoma cells. Cha, H.H., Cram, E.J., Wang, E.C., Huang, A.J., Kasler, H.G., Firestone, G.L. J. Biol. Chem. (1998) [Pubmed]
  3. Role of the increase in p21 in cisplatin-induced acute renal failure in rats. Miyaji, T., Kato, A., Yasuda, H., Fujigaki, Y., Hishida, A. J. Am. Soc. Nephrol. (2001) [Pubmed]
  4. Regulation of cyclin-dependent kinase inhibitors by mitogen-activated protein kinase in angiotensin II-stimulated vascular smooth muscle cell hypertrophy. Liu, Y., Xu, D.L., Wang, M.H., Ouyang, P., Lai, W.Y. Di Yi Jun Yi Da Xue Xue Bao (2002) [Pubmed]
  5. Direct in vivo inhibition of the nuclear cell cycle cascade in experimental mesangial proliferative glomerulonephritis with Roscovitine, a novel cyclin-dependent kinase antagonist. Pippin, J.W., Qu, Q., Meijer, L., Shankland, S.J. J. Clin. Invest. (1997) [Pubmed]
  6. Emi1 is required for cytostatic factor arrest in vertebrate eggs. Reimann, J.D., Jackson, P.K. Nature (2002) [Pubmed]
  7. Requirement for tyrosine phosphorylation of Cdk4 in G1 arrest induced by ultraviolet irradiation. Terada, Y., Tatsuka, M., Jinno, S., Okayama, H. Nature (1995) [Pubmed]
  8. Calmodulin-dependent protein kinase II mediates inactivation of MPF and CSF upon fertilization of Xenopus eggs. Lorca, T., Cruzalegui, F.H., Fesquet, D., Cavadore, J.C., Méry, J., Means, A., Dorée, M. Nature (1993) [Pubmed]
  9. The cdk5/p35 kinase is essential for neurite outgrowth during neuronal differentiation. Nikolic, M., Dudek, H., Kwon, Y.T., Ramos, Y.F., Tsai, L.H. Genes Dev. (1996) [Pubmed]
  10. Homocysteine increases cyclin-dependent kinase in aortic rat tissue. Lubec, B., Labudova, O., Hoeger, H., Muehl, A., Fang-Kircher, S., Marx, M., Mosgoeller, W., Gialamas, J. Circulation (1996) [Pubmed]
  11. Inhibition of cyclin-dependent kinases improves CA1 neuronal survival and behavioral performance after global ischemia in the rat. Wang, F., Corbett, D., Osuga, H., Osuga, S., Ikeda, J.E., Slack, R.S., Hogan, M.J., Hakim, A.M., Park, D.S. J. Cereb. Blood Flow Metab. (2002) [Pubmed]
  12. Differential activation of cyclin and cyclin-dependent kinase genes by adenovirus E1A12S cDNA product. Ishii, T., Shimizu, M., Kanayama, Y., Nakada, S., Nojima, H., Oda, K. Exp. Cell Res. (1993) [Pubmed]
  13. Overexpression of cdk Inhibitor p16INK4a by adenovirus vector inhibits cardiac hypertrophy in vitro and in vivo: a novel strategy for the gene therapy of cardiac hypertrophy. Nozato, T., Ito, H., Watanabe, M., Ono, Y., Adachi, S., Tanaka, H., Hiroe, M., Sunamori, M., Marum, F. J. Mol. Cell. Cardiol. (2001) [Pubmed]
  14. Estrogen-induced rat pituitary tumor is associated with loss of retinoblastoma susceptibility gene product. Chun, T.Y., Wendell, D., Gregg, D., Gorski, J. Mol. Cell. Endocrinol. (1998) [Pubmed]
  15. Cdc2-mediated phosphorylation of the gap junction protein, connexin43, during mitosis. Kanemitsu, M.Y., Jiang, W., Eckhart, W. Cell Growth Differ. (1998) [Pubmed]
  16. Expression of G1 Cell Cycle Regulators in Rat Liver upon Repeated Exposure to Thioacetamide. Kim, K.T., Han, S.Y., Jeong, J.S. The Korean journal of hepatology (2007) [Pubmed]
  17. Tranilast inhibits vascular smooth muscle cell growth and intimal hyperplasia by induction of p21(waf1/cip1/sdi1) and p53. Takahashi, A., Taniguchi, T., Ishikawa, Y., Yokoyama, M. Circ. Res. (1999) [Pubmed]
  18. Membrane-anchored heparin-binding epidermal growth factor-like growth factor acts as a tumor survival factor in a hepatoma cell line. Miyoshi, E., Higashiyama, S., Nakagawa, T., Hayashi, N., Taniguchi, N. J. Biol. Chem. (1997) [Pubmed]
  19. Nerve growth factor induces transcription of the p21 WAF1/CIP1 and cyclin D1 genes in PC12 cells by activating the Sp1 transcription factor. Yan, G.Z., Ziff, E.B. J. Neurosci. (1997) [Pubmed]
  20. p21WAF1 induces permanent growth arrest and enhances differentiation, but does not alter apoptosis in PC12 cells. Erhardt, J.A., Pittman, R.N. Oncogene (1998) [Pubmed]
  21. Oxidative stress induces p21 expression in pancreatic islet cells: possible implication in beta-cell dysfunction. Kaneto, H., Kajimoto, Y., Fujitani, Y., Matsuoka, T., Sakamoto, K., Matsuhisa, M., Yamasaki, Y., Hori, M. Diabetologia (1999) [Pubmed]
  22. Regulation and role of p21 and p27 cyclin-dependent kinase inhibitors during hepatocyte differentiation and growth. Ilyin, G.P., Glaise, D., Gilot, D., Baffet, G., Guguen-Guillouzo, C. Am. J. Physiol. Gastrointest. Liver Physiol. (2003) [Pubmed]
  23. Nitric oxide prevents p21 degradation with the ubiquitin-proteasome pathway in vascular smooth muscle cells. Kibbe, M.R., Nie, S., Seol, D.W., Kovesdi, I., Lizonova, A., Makaroun, M., Billiar, T.R., Tzeng, E. J. Vasc. Surg. (2000) [Pubmed]
  24. Akt/PKB activity is required for Ha-Ras-mediated transformation of intestinal epithelial cells. Sheng, H., Shao, J., DuBois, R.N. J. Biol. Chem. (2001) [Pubmed]
  25. Induction of p53 in the glutamate-induced cell death program. Uberti, D., Grilli, M., Memo, M. Amino Acids (2000) [Pubmed]
  26. A novel role for the cyclin-dependent kinase inhibitor p27(Kip1) in angiotensin II-stimulated vascular smooth muscle cell hypertrophy. Braun-Dullaeus, R.C., Mann, M.J., Ziegler, A., von der Leyen, H.E., Dzau, V.J. J. Clin. Invest. (1999) [Pubmed]
  27. Cell cycle inhibition provides neuroprotection and reduces glial proliferation and scar formation after traumatic brain injury. Di Giovanni, S., Movsesyan, V., Ahmed, F., Cernak, I., Schinelli, S., Stoica, B., Faden, A.I. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  28. Malignant transformation by cyclin E and Ha-Ras correlates with lower sensitivity towards induction of cell death but requires functional Myc and CDK4. Haas, K., Johannes, C., Geisen, C., Schmidt, T., Karsunky, H., Blass-Kampmann, S., Obe, G., Möröy, T. Oncogene (1997) [Pubmed]
  29. Differential regulation of cyclin B1 RNA and protein expression during hepatocyte growth in vivo. Trembley, J.H., Ebbert, J.O., Kren, B.T., Steer, C.J. Cell Growth Differ. (1996) [Pubmed]
  30. Sp1 inhibits proliferation and induces apoptosis in vascular smooth muscle cells by repressing p21WAF1/Cip1 transcription and cyclin D1-Cdk4-p21WAF1/Cip1 complex formation. Kavurma, M.M., Khachigian, L.M. J. Biol. Chem. (2003) [Pubmed]
  31. Role of JNK, p38, and ERK in platelet-derived growth factor-induced vascular proliferation, migration, and gene expression. Zhan, Y., Kim, S., Izumi, Y., Izumiya, Y., Nakao, T., Miyazaki, H., Iwao, H. Arterioscler. Thromb. Vasc. Biol. (2003) [Pubmed]
  32. Peroxisome proliferator-activated receptor gamma ligands inhibit retinoblastoma phosphorylation and G1--> S transition in vascular smooth muscle cells. Wakino, S., Kintscher, U., Kim, S., Yin, F., Hsueh, W.A., Law, R.E. J. Biol. Chem. (2000) [Pubmed]
  33. Inactivation of the cyclin-dependent kinase inhibitor p27 upon loss of the tuberous sclerosis complex gene-2. Soucek, T., Yeung, R.S., Hengstschläger, M. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  34. Oncogenic transformation of cells by a conditionally active form of the protein kinase Akt/PKB. Mirza, A.M., Kohn, A.D., Roth, R.A., McMahon, M. Cell Growth Differ. (2000) [Pubmed]
  35. HES-1 repression of differentiation and proliferation in PC12 cells: role for the helix 3-helix 4 domain in transcription repression. Castella, P., Sawai, S., Nakao, K., Wagner, J.A., Caudy, M. Mol. Cell. Biol. (2000) [Pubmed]
  36. Adenovirus-mediated delivery of fas ligand inhibits intimal hyperplasia after balloon injury in immunologically primed animals. Luo, Z., Sata, M., Nguyen, T., Kaplan, J.M., Akita, G.Y., Walsh, K. Circulation (1999) [Pubmed]
  37. p27 cytoplasmic localization is regulated by phosphorylation on Ser10 and is not a prerequisite for its proteolysis. Rodier, G., Montagnoli, A., Di Marcotullio, L., Coulombe, P., Draetta, G.F., Pagano, M., Meloche, S. EMBO J. (2001) [Pubmed]
  38. The carcinogen 2-acetylaminofluorene inhibits activation and nuclear accumulation of cyclin-dependent kinase 2 in growth-induced rat liver. Lindeman, B., Skarpen, E., Oksvold, M.P., Huitfeldt, H.S. Mol. Carcinog. (2000) [Pubmed]
  39. Intimal hyperplasia after vascular injury is inhibited by antisense cdk 2 kinase oligonucleotides. Morishita, R., Gibbons, G.H., Ellison, K.E., Nakajima, M., von der Leyen, H., Zhang, L., Kaneda, Y., Ogihara, T., Dzau, V.J. J. Clin. Invest. (1994) [Pubmed]
  40. Cyclin-dependent kinases as a therapeutic target for stroke. Osuga, H., Osuga, S., Wang, F., Fetni, R., Hogan, M.J., Slack, R.S., Hakim, A.M., Ikeda, J.E., Park, D.S. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  41. SCR: novel human suppressors of cdc2/cdc13 mutants of Schizosaccharomyces pombe harbour motifs for RNA binding proteins. Kanaoka, Y., Nojima, H. Nucleic Acids Res. (1994) [Pubmed]
  42. Discordant hepatic expression of the cell division control enzyme p34cdc2 kinase, proliferating cell nuclear antigen, p53 tumor suppressor protein, and p21Waf1 cyclin-dependent kinase inhibitory protein after WY14,643 ([4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid) dosing to rats. Ma, X., Stoffregen, D.A., Wheelock, G.D., Rininger, J.A., Babish, J.G. Mol. Pharmacol. (1997) [Pubmed]
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