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Gene Review

Cdk6  -  cyclin-dependent kinase 6

Mus musculus

Synonyms: 5830411I20, AI504062, CR2 protein kinase, CRK2, Cdkn6, ...
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Disease relevance of Cdk6

  • Our findings support the concept that pharmacologic inhibition of Cdk4/Cdk6 may represent a useful therapeutic strategy to control cell proliferation and possibly promote myogenic differentiation in rhabdomyosarcoma [1].
  • This result suggests that deregulated expression of Cdk6 and cyclinD3 may predispose cells to malignant transformation, supporting the recent finding that cyclin D3 activated by chromosomal rearrangement is the causative gene of non-Hodgkin B lymphoma, in which Cdk6 is the major partner kinase [2].
  • Both CR-K1 and CR-K2 were characterized as possessing high affinity towards 13,14-dihydro-15-ketoprostaglandin F2 alpha and were localized immunohistochemically in the zona glomerulosa and the zona reticularis of adrenal cortex, and in the ganglion cell of adrenal medulla [3].

High impact information on Cdk6


Biological context of Cdk6


Anatomical context of Cdk6

  • Cyclin D-dependent Cdk4 and Cdk6 were expressed in most of a panel of six human rhabdomyosarcoma-derived cell lines [1].
  • The enforced expression of Cdk6 blocked BMP-2-induced osteoblast differentiation to various degrees, depending on the level of its overexpression [6].
  • We describe here that 2-5-fold overexpression of both Cdk6 and D3 enhances by 5x10(3)-10(6)-fold the susceptibility of the BALB/c3T3 and C3H10T1/2 mouse fibroblast lines to ultraviolet irradiation- as well as 3-methylcholanthrene-induced transformation [2].
  • To determine the direct effect of Cdk6 on osteoclast differentiation, stable clones of RAW cells transfected with Cdk6 cDNA were established [9].
  • No substantial changes in Cdk2 or Cdk6 distribution and kinase activities were detected in spinal motor neurons from SOD1(G37R) mice when compared with normal mice [10].

Associations of Cdk6 with chemical compounds


Regulatory relationships of Cdk6

  • RESULTS AND CONCLUSION: Among the cell cycle factors examined, the Cdk6 level was downregulated by RANKL synchronously with the appearance of multinucleated osteoclasts [9].

Other interactions of Cdk6


  1. 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]
  2. Overexpression of Cdk6-cyclin D3 highly sensitizes cells to physical and chemical transformation. Chen, Q., Lin, J., Jinno, S., Okayama, H. Oncogene (2003) [Pubmed]
  3. Purification and properties of six aldo-keto reductases from rat adrenal gland. Inazu, N., Nagashima, Y., Satoh, T., Fujii, T. J. Biochem. (1994) [Pubmed]
  4. Mammalian cells cycle without the D-type cyclin-dependent kinases Cdk4 and Cdk6. Malumbres, M., Sotillo, R., Santamaría, D., Galán, J., Cerezo, A., Ortega, S., Dubus, P., Barbacid, M. Cell (2004) [Pubmed]
  5. Mammalian cyclin-dependent kinases. Malumbres, M., Barbacid, M. Trends Biochem. Sci. (2005) [Pubmed]
  6. Bone morphogenetic protein 2-induced osteoblast differentiation requires Smad-mediated down-regulation of Cdk6. Ogasawara, T., Kawaguchi, H., Jinno, S., Hoshi, K., Itaka, K., Takato, T., Nakamura, K., Okayama, H. Mol. Cell. Biol. (2004) [Pubmed]
  7. 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]
  8. Cell cycle and cancer: genetic analysis of the role of cyclin-dependent kinases. Barbacid, M., Ortega, S., Sotillo, R., Odajima, J., Martín, A., Santamaría, D., Dubus, P., Malumbres, M. Cold Spring Harb. Symp. Quant. Biol. (2005) [Pubmed]
  9. Osteoclast differentiation by RANKL requires NF-kappaB-mediated downregulation of cyclin-dependent kinase 6 (Cdk6). Ogasawara, T., Katagiri, M., Yamamoto, A., Hoshi, K., Takato, T., Nakamura, K., Tanaka, S., Okayama, H., Kawaguchi, H. J. Bone Miner. Res. (2004) [Pubmed]
  10. Cell cycle regulators in the neuronal death pathway of amyotrophic lateral sclerosis caused by mutant superoxide dismutase 1. Nguyen, M.D., Boudreau, M., Kriz, J., Couillard-Després, S., Kaplan, D.R., Julien, J.P. J. Neurosci. (2003) [Pubmed]
  11. Cdk6-cyclin D3 activity in murine ES cells is resistant to inhibition by p16(INK4a). Faast, R., White, J., Cartwright, P., Crocker, L., Sarcevic, B., Dalton, S. Oncogene (2004) [Pubmed]
  12. Regulation of G(1) cyclin-dependent kinases in the mammalian cell cycle. Ekholm, S.V., Reed, S.I. Curr. Opin. Cell Biol. (2000) [Pubmed]
  13. Cellular response to oncogenic ras involves induction of the Cdk4 and Cdk6 inhibitor p15(INK4b). Malumbres, M., Pérez De Castro, I., Hernández, M.I., Jiménez, M., Corral, T., Pellicer, A. Mol. Cell. Biol. (2000) [Pubmed]
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