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Gene Review

Cdk1  -  cyclin-dependent kinase 1

Mus musculus

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


High impact information on Cdc2a

  • Entry into mitosis requires the activation of cdk1/cyclin B, while mitotic exit is achieved when the same kinase activity decreases, as cyclin B is degraded [6].
  • In a wide variety of animal species, oocyte maturation is arrested temporarily at prophase of meiosis I (ref. 1). Resumption of meiosis requires activation of cyclin-dependent kinase-1 (CDK1, p34cdc2), one component of maturation-promoting factor (MPF) [7].
  • Trrap-deficient cells fail to sustain mitotic arrest despite chromosome missegregation and disrupted spindles, and display compromised cdk1 activity [8].
  • Meiosis arrest in Ccna1-/- males was associated with increased germ cell apoptosis, desynapsis abnormalities and reduction of Cdc2 kinase activation at the end of meiotic prophase [9].
  • Cyclin A2 activates cdc2 (Cdk1) on passage into mitosis and Cdk2 at the G1/S transition [10].

Chemical compound and disease context of Cdc2a


Biological context of Cdc2a

  • Moreover, the significant reduction in hepatocyte mitosis was associated with diminished mRNA levels and nuclear expression of Cdc25B phosphatase and delayed accumulation of cyclin B1 protein, which is required for Cdk1 activation and entry into mitosis [16].
  • As a result, cyclin-dependent kinase activity, Rb phosphorylation, and E2F target gene expression were restored to nearly normal levels, rendering cells responsive to normal growth signals [17].
  • Cyclin a-CDK phosphorylation regulates MDM2 protein interactions [18].
  • This is the first description that p130 may have a role in inhibiting CDK activity during senescence [19].
  • The current studies address whether regulation of the cell cycle during lens fiber differentiation in normal lenses or in lenses in which pRB has been inactivated is accompanied by changes in expression of cyclin and cyclin-dependent kinase genes [20].

Anatomical context of Cdc2a

  • Foxo3a was also found to facilitate the nuclear localization of p27(kip1) in oocytes, a cyclin-dependent kinase (Cdk) inhibitor that may serve to inhibit oocyte growth [21].
  • Density-arrested fibroblasts contain low levels of cyclins E and A, and high levels of the Cdk inhibitor p27kip1 [22].
  • In this study we showed that inducing apoptosis in mouse mesangial cells with ultraviolet (UV) irradiation was associated with increased cyclin A-cyclin dependent kinase (CDK) 2 activity [23].
  • Immunohistochemical detection of Cdk1 was most apparent in early pachytene spermatocytes, while staining intensity diminished in diplotene and meiotically dividing spermatocytes, the cells in which cyclin A1 expression was strongest [24].
  • All five Cdk family genes examined were expressed in Sertoli cells of the adult testis, which are no longer mitotically active [25].

Associations of Cdc2a with chemical compounds


Physical interactions of Cdc2a


Enzymatic interactions of Cdc2a


Regulatory relationships of Cdc2a


Other interactions of Cdc2a


Analytical, diagnostic and therapeutic context of Cdc2a


  1. p21 and mTERT are novel markers for determining different ischemic time periods in renal ischemia-reperfusion injury. Hochegger, K., Koppelstaetter, C., Tagwerker, A., Huber, J.M., Heininger, D., Mayer, G., Rosenkranz, A.R. Am. J. Physiol. Renal Physiol. (2007) [Pubmed]
  2. Pharmacologic inhibition of cyclin-dependent kinase 4/6 activity arrests proliferation in myoblasts and rhabdomyosarcoma-derived cells. Saab, R., Bills, J.L., Miceli, A.P., Anderson, C.M., Khoury, J.D., Fry, D.W., Navid, F., Houghton, P.J., Skapek, S.X. Mol. Cancer Ther. (2006) [Pubmed]
  3. Multiple cyclin-dependent kinases signals are critical mediators of ischemia/hypoxic neuronal death in vitro and in vivo. Rashidian, J., Iyirhiaro, G., Aleyasin, H., Rios, M., Vincent, I., Callaghan, S., Bland, R.J., Slack, R.S., During, M.J., Park, D.S. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  4. The cyclin-dependent kinase inhibitor p27 (Kip1) regulates both DNA synthesis and apoptosis in mammary epithelium but is not required for its functional development during pregnancy. Davison, E.A., Lee, C.S., Naylor, M.J., Oakes, S.R., Sutherland, R.L., Hennighausen, L., Ormandy, C.J., Musgrove, E.A. Mol. Endocrinol. (2003) [Pubmed]
  5. Mitotic cell cycle proteins increase in podocytes despite lack of proliferation. Petermann, A.T., Pippin, J., Hiromura, K., Monkawa, T., Durvasula, R., Couser, W.G., Kopp, J., Shankland, S.J. Kidney Int. (2003) [Pubmed]
  6. Tome-1, a trigger of mitotic entry, is degraded during G1 via the APC. Ayad, N.G., Rankin, S., Murakami, M., Jebanathirajah, J., Gygi, S., Kirschner, M.W. Cell (2003) [Pubmed]
  7. Cdc25b phosphatase is required for resumption of meiosis during oocyte maturation. Lincoln, A.J., Wickramasinghe, D., Stein, P., Schultz, R.M., Palko, M.E., De Miguel, M.P., Tessarollo, L., Donovan, P.J. Nat. Genet. (2002) [Pubmed]
  8. Disruption of Trrap causes early embryonic lethality and defects in cell cycle progression. Herceg, Z., Hulla, W., Gell, D., Cuenin, C., Lleonart, M., Jackson, S., Wang, Z.Q. Nat. Genet. (2001) [Pubmed]
  9. Cyclin A1 is required for meiosis in the male mouse. Liu, D., Matzuk, M.M., Sung, W.K., Guo, Q., Wang, P., Wolgemuth, D.J. Nat. Genet. (1998) [Pubmed]
  10. Delayed early embryonic lethality following disruption of the murine cyclin A2 gene. Murphy, M., Stinnakre, M.G., Senamaud-Beaufort, C., Winston, N.J., Sweeney, C., Kubelka, M., Carrington, M., Bréchot, C., Sobczak-Thépot, J. Nat. Genet. (1997) [Pubmed]
  11. Angiotensin converting-enzyme inhibitor treatment reduces glomerular p16INK4 and p27Kip1 expression in diabetic BBdp rats. Wolf, G., Wenzel, U., Ziyadeh, F.N., Stahl, R.A. Diabetologia (1999) [Pubmed]
  12. Induction of 32- and 34-kDa stress proteins by sodium arsenite, heavy metals, and thiol-reactive agents. Caltabiano, M.M., Koestler, T.P., Poste, G., Greig, R.G. J. Biol. Chem. (1986) [Pubmed]
  13. Reversal of collapsing glomerulopathy in mice with the cyclin-dependent kinase inhibitor CYC202. Gherardi, D., D'Agati, V., Chu, T.H., Barnett, A., Gianella-Borradori, A., Gelman, I.H., Nelson, P.J. J. Am. Soc. Nephrol. (2004) [Pubmed]
  14. Isolation and immunological characterization of the mammalian 32-/34-kDa stress protein. Caltabiano, M.M., Poste, G., Greig, R.G. Exp. Cell Res. (1988) [Pubmed]
  15. Coordination of the cell cycle is an important determinant of the syndrome of acute renal failure. Megyesi, J., Andrade, L., Vieira, J.M., Safirstein, R.L., Price, P.M. Am. J. Physiol. Renal Physiol. (2002) [Pubmed]
  16. The Forkhead Box m1b transcription factor is essential for hepatocyte DNA replication and mitosis during mouse liver regeneration. Wang, X., Kiyokawa, H., Dennewitz, M.B., Costa, R.H. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  17. E2f1, E2f2, and E2f3 control E2F target expression and cellular proliferation via a p53-dependent negative feedback loop. Timmers, C., Sharma, N., Opavsky, R., Maiti, B., Wu, L., Wu, J., Orringer, D., Trikha, P., Saavedra, H.I., Leone, G. Mol. Cell. Biol. (2007) [Pubmed]
  18. Cyclin a-CDK phosphorylation regulates MDM2 protein interactions. Zhang, T., Prives, C. J. Biol. Chem. (2001) [Pubmed]
  19. Inhibition of the phosphoinositide 3-kinase pathway induces a senescence-like arrest mediated by p27Kip1. Collado, M., Medema, R.H., Garcia-Cao, I., Dubuisson, M.L., Barradas, M., Glassford, J., Rivas, C., Burgering, B.M., Serrano, M., Lam, E.W. J. Biol. Chem. (2000) [Pubmed]
  20. Regulation of cyclin and cyclin-dependent kinase gene expression during lens differentiation requires the retinoblastoma protein. Fromm, L., Overbeek, P.A. Oncogene (1996) [Pubmed]
  21. Infertility caused by retardation of follicular development in mice with oocyte-specific expression of Foxo3a. Liu, L., Rajareddy, S., Reddy, P., Du, C., Jagarlamudi, K., Shen, Y., Gunnarsson, D., Selstam, G., Boman, K., Liu, K. Development (2007) [Pubmed]
  22. Differential modulation of G1 cyclins and the Cdk inhibitor p27kip1 by platelet-derived growth factor and plasma factors in density-arrested fibroblasts. Winston, J., Dong, F., Pledger, W.J. J. Biol. Chem. (1996) [Pubmed]
  23. The subcellular localization of cyclin dependent kinase 2 determines the fate of mesangial cells: role in apoptosis and proliferation. Hiromura, K., Pippin, J.W., Blonski, M.J., Roberts, J.M., Shankland, S.J. Oncogene (2002) [Pubmed]
  24. Regulation of meiosis during mammalian spermatogenesis: the A-type cyclins and their associated cyclin-dependent kinases are differentially expressed in the germ-cell lineage. Ravnik, S.E., Wolgemuth, D.J. Dev. Biol. (1999) [Pubmed]
  25. Cdk family genes are expressed not only in dividing but also in terminally differentiated mouse germ cells, suggesting their possible function during both cell division and differentiation. Rhee, K., Wolgemuth, D.J. Dev. Dyn. (1995) [Pubmed]
  26. Gene expression of cyclin-dependent kinase inhibitors and effect of heparin on their expression in mice with hypoxia-induced pulmonary hypertension. Yu, L., Quinn, D.A., Garg, H.G., Hales, C.A. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  27. PKB/AKT is involved in resumption of meiosis in mouse oocytes. Kalous, J., Solc, P., Baran, V., Kubelka, M., Schultz, R.M., Motlik, J. Biol. Cell (2006) [Pubmed]
  28. Differential effect of silibinin on E2F transcription factors and associated biological events in chronically UVB-exposed skin versus tumors in SKH-1 hairless mice. Gu, M., Singh, R.P., Dhanalakshmi, S., Mohan, S., Agarwal, R. Mol. Cancer Ther. (2006) [Pubmed]
  29. The FT210 cell line is a mouse G2 phase mutant with a temperature-sensitive CDC2 gene product. Th'ng, J.P., Wright, P.S., Hamaguchi, J., Lee, M.G., Norbury, C.J., Nurse, P., Bradbury, E.M. Cell (1990) [Pubmed]
  30. p57(Kip2) stabilizes the MyoD protein by inhibiting cyclin E-Cdk2 kinase activity in growing myoblasts. Reynaud, E.G., Pelpel, K., Guillier, M., Leibovitch, M.P., Leibovitch, S.A. Mol. Cell. Biol. (1999) [Pubmed]
  31. Krüppel-like factor 5 promotes mitosis by activating the cyclin B1/Cdc2 complex during oncogenic Ras-mediated transformation. Nandan, M.O., Chanchevalap, S., Dalton, W.B., Yang, V.W. FEBS Lett. (2005) [Pubmed]
  32. Cyclin D1 overexpression promotes cardiomyocyte DNA synthesis and multinucleation in transgenic mice. Soonpaa, M.H., Koh, G.Y., Pajak, L., Jing, S., Wang, H., Franklin, M.T., Kim, K.K., Field, L.J. J. Clin. Invest. (1997) [Pubmed]
  33. p27Kip1 and p130 cooperate to regulate hematopoietic cell proliferation in vivo. Soeiro, I., Mohamedali, A., Romanska, H.M., Lea, N.C., Child, E.S., Glassford, J., Orr, S.J., Roberts, C., Naresh, K.N., Lalani, e.l.-.N., Mann, D.J., Watson, R.J., Thomas, N.S., Lam, E.W. Mol. Cell. Biol. (2006) [Pubmed]
  34. Cyclin D1 overexpression in mouse epidermis increases cyclin-dependent kinase activity and cell proliferation in vivo but does not affect skin tumor development. Rodriguez-Puebla, M.L., LaCava, M., Conti, C.J. Cell Growth Differ. (1999) [Pubmed]
  35. Kainate receptor-mediated apoptosis in primary cultures of cerebellar granule cells is attenuated by mitogen-activated protein and cyclin-dependent kinase inhibitors. Giardina, S.F., Beart, P.M. Br. J. Pharmacol. (2002) [Pubmed]
  36. Changes in motility, gene expression and actin dynamics: Cdk6-induced cytoskeletal changes associated with differentiation in mouse astrocytes. Slomiany, P., Baker, T., Elliott, E.R., Grossel, M.J. J. Cell. Biochem. (2006) [Pubmed]
  37. Pak1 phosphorylation on t212 affects microtubules in cells undergoing mitosis. Banerjee, M., Worth, D., Prowse, D.M., Nikolic, M. Curr. Biol. (2002) [Pubmed]
  38. Either cyclin B1 or B2 is necessary and sufficient for inducing germinal vesicle breakdown during frog (Rana japonica) oocyte maturation. Ihara, J., Yoshida, N., Tanaka, T., Mita, K., Yamashita, M. Mol. Reprod. Dev. (1998) [Pubmed]
  39. p19ARF prevents G1 cyclin-dependent kinase activation by interacting with MDM2 and activating p53 in mouse fibroblasts. Kurokawa, K., Tanaka, T., Kato, J. Oncogene (1999) [Pubmed]
  40. Cdc2-cyclin E complexes regulate the G1/S phase transition. Aleem, E., Kiyokawa, H., Kaldis, P. Nat. Cell Biol. (2005) [Pubmed]
  41. Developmental activation of the Rb-E2F pathway and establishment of cell cycle-regulated cyclin-dependent kinase activity during embryonic stem cell differentiation. White, J., Stead, E., Faast, R., Conn, S., Cartwright, P., Dalton, S. Mol. Biol. Cell (2005) [Pubmed]
  42. Up-regulation of c-myc induces the gene expression of the murine homologues of p34cdc2 and cyclin-dependent kinase-2 in T lymphocytes. Kim, Y.H., Buchholz, M.A., Chrest, F.J., Nordin, A.A. J. Immunol. (1994) [Pubmed]
  43. Cyclin proteolysis and CDK inhibitors: two redundant pathways to maintain genome stability in mammalian cells. Chibazakura, T. Cell Cycle (2004) [Pubmed]
  44. p18(INK4c) collaborates with other CDK-inhibitory proteins in the regenerating liver. Luedde, T., Rodriguez, M.E., Tacke, F., Xiong, Y., Brenner, D.A., Trautwein, C. Hepatology (2003) [Pubmed]
  45. The retinoblastoma protein alters the phosphorylation state of polyomavirus large T antigen in murine cell extracts and inhibits polyomavirus origin DNA replication. Reynisdóttir, I., Bhattacharyya, S., Zhang, D., Prives, C. J. Virol. (1999) [Pubmed]
  46. Cell cycle regulatory proteins in the liver in murine Trypanosoma cruzi infection. Bouzahzah, B., Nagajyothi, F., Desruisseaux, M.S., Krishnamachary, M., Factor, S.M., Cohen, A.W., Lisanti, M.P., Petkova, S.B., Pestell, R.G., Wittner, M., Mukherjee, S., Weiss, L.M., Jelicks, L.A., Albanese, C., Tanowitz, H.B. Cell Cycle (2006) [Pubmed]
  47. Myc and Ras collaborate in inducing accumulation of active cyclin E/Cdk2 and E2F. Leone, G., DeGregori, J., Sears, R., Jakoi, L., Nevins, J.R. Nature (1997) [Pubmed]
  48. Involvement of p21 and p27 in the regulation of CDK activity and cell cycle progression in the regenerating liver. Albrecht, J.H., Poon, R.Y., Ahonen, C.L., Rieland, B.M., Deng, C., Crary, G.S. Oncogene (1998) [Pubmed]
  49. Protein kinase A regulates cell cycle progression of mouse fertilized eggs by means of MPF. Yu, B., Wang, Y., Liu, Y., Liu, Y., Li, X., Wu, D., Zong, Z., Zhang, J., Yu, D. Dev. Dyn. (2005) [Pubmed]
  50. cdc2 is a component of the M phase-specific histone H1 kinase: evidence for identity with MPF. Arion, D., Meijer, L., Brizuela, L., Beach, D. Cell (1988) [Pubmed]
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