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Gene Review

Cdk2  -  cyclin-dependent kinase 2

Mus musculus

Synonyms: A630093N05Rik, Cdkn2, Cell division protein kinase 2, Cyclin-dependent kinase 2
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Disease relevance of Cdk2


High impact information on Cdk2


Chemical compound and disease context of Cdk2

  • RESULTS: Inhibiting CDK2 activity resulted in a marked decrease in glomerular DNA synthesis [5-bromo-2'-deoxyridine (BrdU) staining] in Roscovitine-treated animals at day 5 of nephritis (P < 0.05 versus control) [8].
  • METHODS: To determine if decreasing podocyte proliferation improves renal function, CDK2 activity was reduced with the purine analogue roscovitine in mice with antibody-induced experimental glomerulonephritis [8].

Biological context of Cdk2

  • Furthermore, increased nuclear p21 levels and reduced expression of Cdc25A phosphatase coincided with decreases in Cdk2 activation and hepatocyte progression into S-phase [9].
  • Together, these findings demonstrate a novel mechanism underlying the DNA damage-induced G(1) arrest of hematopoietic cells, that is, inhibition of Cdk2 phosphorylation and activation [10].
  • Notably, the PI 3-kinase inhibitor, LY294002, completely blocked cytokine-induced Cdk2 activation and cell growth in irradiated 32D cells but not in nonirradiated cells [10].
  • By contrast, ectopic expression of the Cdk2/Cdk4 interaction-deficient Delta177-191 mutant promotes differentiation and induces gene expression as effectively as wild-type C/EBPalpha [11].
  • Thus, the integrity of the transactivation and DNA binding domains, but not of the Cdk2/Cdk4 interaction region, is necessary for C/EBPalpha-induced differentiation [11].

Anatomical context of Cdk2


Associations of Cdk2 with chemical compounds

  • These results suggest that p27Kip1 CKI is a critical target in the initial response of cancer cells to androgen depletion and plays a key role in Cdk2 inactivation through association with the kinase complex, leading to cell cycle arrest [17].
  • The administration of ASA to DAB treated animals induced Cdk2 (29%) [18].
  • Furthermore, CTalpha expression is decreased in cells overexpressing a dominant-negative form of CDK2 and in cells treated with the CDK2 kinase inhibitors roscovitine and olomoucine [19].
  • In addition, the NH2 domain of p57(Kip2) necessary for inhibition of cyclin E-Cdk2 activity was sufficient to inhibit MyoD phosphorylation and to stabilize it, leading to its accumulation in proliferative myoblasts [16].
  • Levels of the closely related Cdk2 inhibitor, p21(Cip1), are unaffected by cicaprost [20].

Physical interactions of Cdk2

  • Immunoprecipitates of cyclin E1 complexes from Cdk2(-/-) spleen extracts displayed no activity toward histone H1 [21].
  • Accordingly, co-expression with cyclin A/Cdk2 in cells did not inhibit the DNA binding and transcriptional activities of CDP/Cux p110 [22].
  • Cyclin D1/cdk2 kinase is present in a G1 phase-specific protein complex Yi1 that binds to the mouse thymidine kinase gene promoter [23].
  • Moreover, these mutants of p27Kip1 are also impaired in disrupting the interaction between cyclin/cdk2 and the repressor complexes of E2Fs [24].
  • By gel mobility shift, E2F1 was found in P2 c-myc band shift complexes along with the cyclin-dependent kinase 2 [25].

Regulatory relationships of Cdk2


Other interactions of Cdk2

  • Changes in rates of cell division, cell cycle structure and the establishment of cell cycle-regulated Cdk2 activity can therefore be explained by activation of the E2F-pRb pathway [26].
  • Yi1 contains cyclin D1/cdk2 kinase as shown by using specific antibodies to cyclins, cdks and the Yi1 DNA-binding protein in gel retardation, western blotting, and immunoprecipitation assays [23].
  • Mouse knockouts of Cdk2 and Cdk4 have demonstrated that, individually, these genes are not essential for viability [31].
  • Cytokine treatment of irradiated cells induced Cdk2 phosphorylation and activation, and cells entered into S phase despite sustained high-level expression of p21 and p27 [10].
  • Our in vivo results provide strong evidence that Cdc2 may compensate the loss of Cdk2 function [32].

Analytical, diagnostic and therapeutic context of Cdk2


  1. Mammalian cyclin-dependent kinases. Malumbres, M., Barbacid, M. Trends Biochem. Sci. (2005) [Pubmed]
  2. Cell cycle control with minimal participation of Cdk2 in a murine fibrosarcoma clone cultured in protein-free medium. Dobashi, Y., Chigira, M., Shoji, M., Wakata, Y., Kitagawa, M., Tamauchi, H., Akiyama, T., Kameya, T. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  3. Cdk2 is dispensable for cell cycle inhibition and tumor suppression mediated by p27(Kip1) and p21(Cip1). Martín, A., Odajima, J., Hunt, S.L., Dubus, P., Ortega, S., Malumbres, M., Barbacid, M. Cancer Cell (2005) [Pubmed]
  4. Histone H1 phosphorylation by Cdk2 selectively modulates mouse mammary tumor virus transcription through chromatin remodeling. Bhattacharjee, R.N., Banks, G.C., Trotter, K.W., Lee, H.L., Archer, T.K. Mol. Cell. Biol. (2001) [Pubmed]
  5. G1 phase-specific suppression of the Cdk2 activity by ginsenoside Rh2 in cultured murine cells. Ota, T., Maeda, M., Odashima, S., Ninomiya-Tsuji, J., Tatsuka, M. Life Sci. (1997) [Pubmed]
  6. Cyclin-dependent kinase 2 is essential for meiosis but not for mitotic cell division in mice. Ortega, S., Prieto, I., Odajima, J., Martín, A., Dubus, P., Sotillo, R., Barbero, J.L., Malumbres, M., Barbacid, M. Nat. Genet. (2003) [Pubmed]
  7. The mouse Mps1p-like kinase regulates centrosome duplication. Fisk, H.A., Winey, M. Cell (2001) [Pubmed]
  8. Limitation of podocyte proliferation improves renal function in experimental crescentic glomerulonephritis. Griffin, S.V., Krofft, R.D., Pippin, J.W., Shankland, S.J. Kidney Int. (2005) [Pubmed]
  9. 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]
  10. Dna damage-induced G(1) arrest in hematopoietic cells is overridden following phosphatidylinositol 3-kinase-dependent activation of cyclin-dependent kinase 2. Eapen, A.K., Henry, M.K., Quelle, D.E., Quelle, F.W. Mol. Cell. Biol. (2001) [Pubmed]
  11. Transcription activation function of C/EBPalpha is required for induction of granulocytic differentiation. Keeshan, K., Santilli, G., Corradini, F., Perrotti, D., Calabretta, B. Blood (2003) [Pubmed]
  12. Analysis of cell cycle arrest in adipocyte differentiation. Reichert, M., Eick, D. Oncogene (1999) [Pubmed]
  13. Murine coronavirus replication induces cell cycle arrest in G0/G1 phase. Chen, C.J., Makino, S. J. Virol. (2004) [Pubmed]
  14. 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]
  15. The cyclin-dependent kinase inhibitors p27Kip1 and p21Cip1 are not essential in T cell anergy. Verdoodt, B., Blazek, T., Rauch, P., Schuler, G., Steinkasserer, A., Lutz, M.B., Funk, J.O. Eur. J. Immunol. (2003) [Pubmed]
  16. 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]
  17. Critical role for p27Kip1 in cell cycle arrest after androgen depletion in mouse mammary carcinoma cells (SC-3). Menjo, M., Kaneko, Y., Ogata, E., Ikeda, K., Nakanishi, M. Oncogene (1998) [Pubmed]
  18. Cell cycle arrest and modulation of HO-1 expression induced by acetyl salicylic acid in hepatocarcinogenesis. Sacca, P., Caballero, F., Batlle, A., Vazquez, E. Int. J. Biochem. Cell Biol. (2004) [Pubmed]
  19. Phosphorylation of Sp1 by cyclin-dependent kinase 2 modulates the role of Sp1 in CTP:phosphocholine cytidylyltransferase alpha regulation during the S phase of the cell cycle. Banchio, C., Schang, L.M., Vance, D.E. J. Biol. Chem. (2004) [Pubmed]
  20. Antimitogenesis linked to regulation of Skp2 gene expression. Stewart, S.A., Kothapalli, D., Yung, Y., Assoian, R.K. J. Biol. Chem. (2004) [Pubmed]
  21. Cdk2 knockout mice are viable. Berthet, C., Aleem, E., Coppola, V., Tessarollo, L., Kaldis, P. Curr. Biol. (2003) [Pubmed]
  22. Differential regulation of CDP/Cux p110 by cyclin A/Cdk2 and cyclin A/Cdk1. Santaguida, M., Nepveu, A. J. Biol. Chem. (2005) [Pubmed]
  23. Cyclin D1/cdk2 kinase is present in a G1 phase-specific protein complex Yi1 that binds to the mouse thymidine kinase gene promoter. Dou, Q.P., Molnar, G., Pardee, A.B. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  24. p27Kip1 induces an accumulation of the repressor complexes of E2F and inhibits expression of the E2F-regulated genes. Shiyanov, P., Hayes, S., Chen, N., Pestov, D.G., Lau, L.F., Raychaudhuri, P. Mol. Biol. Cell (1997) [Pubmed]
  25. Role for E2F1 in p210 BCR-ABL downstream regulation of c-myc transcription initiation. Studies in murine myeloid cells. Stewart, M.J., Litz-Jackson, S., Burgess, G.S., Williamson, E.A., Leibowitz, D.S., Boswell, H.S. Leukemia (1995) [Pubmed]
  26. 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]
  27. 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]
  28. The appearance of truncated cyclin A2 correlates with differentiation of mouse embryonic stem cells. Anger, M., Bryja, V., Jirmanova, L., Hampl, A., Carrington, M., Motlik, J., Dvorak, P., Kubelka, M. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  29. Antisense Cdk2 kinase oligodeoxynucleotide inhibits ICAM-1 expression in murine cardiac allograft arteriopathy. Suzuki, J., Isobe, M., Morishita, R., Aoki, M., Yamazaki, S., Kaneda, Y., Sawa, Y., Matsuda, H., Ogihara, T., Horie, S., Okubo, Y., Sekiguchi, M. Transplant. Proc. (1998) [Pubmed]
  30. Genetic substitution of Cdk1 by Cdk2 leads to embryonic lethality and loss of meiotic function of Cdk2. Satyanarayana, A., Berthet, C., Lopez-Molina, J., Coppola, V., Tessarollo, L., Kaldis, P. Development (2008) [Pubmed]
  31. Combined loss of cdk2 and cdk4 results in embryonic lethality and rb hypophosphorylation. Berthet, C., Klarmann, K.D., Hilton, M.B., Suh, H.C., Keller, J.R., Kiyokawa, H., Kaldis, P. Dev. Cell (2006) [Pubmed]
  32. Cdc2-cyclin E complexes regulate the G1/S phase transition. Aleem, E., Kiyokawa, H., Kaldis, P. Nat. Cell Biol. (2005) [Pubmed]
  33. Cell cycle-specific induction of Cdk2 expression in B lymphocytes following antigen receptor cross-linking. Tanguay, D.A., Chiles, T.C. Mol. Immunol. (1994) [Pubmed]
  34. Cell attachment to the extracellular matrix induces proteasomal degradation of p21(CIP1) via Cdc42/Rac1 signaling. Bao, W., Thullberg, M., Zhang, H., Onischenko, A., Strömblad, S. Mol. Cell. Biol. (2002) [Pubmed]
  35. Regulation of B cell function by the immunosuppressive agent leflunomide. Siemasko, K.F., Chong, A.S., Williams, J.W., Bremer, E.G., Finnegan, A. Transplantation (1996) [Pubmed]
  36. Downregulation of endothelin expression in allograft coronary arteries after gene therapy targeting Cdk2 kinase. Isobe, M., Suzuki, J., Morishita, R., Kaneda, Y., Sawa, Y., Matsuda, H., Ogihara, T., Horie, S., Okubo, Y., Amano, J. Transplant. Proc. (1998) [Pubmed]
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