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Gene Review

Cdk4  -  Cyclin-dependent kinase 4

Drosophila melanogaster

Synonyms: 8-6, CDK4, CDK4/6, CG5072, Cdk4/6, ...
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Disease relevance of Cdk4


High impact information on Cdk4

  • The Drosophila melanogaster cyclin-dependent protein kinase complex CycD/Cdk4 stimulates both cell cycle progression and cell growth (accumulation of mass) [2].
  • The Drosophila mitochondrial ribosomal protein mRpL12 is required for Cyclin D/Cdk4-driven growth [2].
  • Our results indicate, therefore, that progression into and through the cell cycle can occur in the absence of Cdk4 [3].
  • These results suggest that the ability of Cyclin D/Cdk4 to drive growth in the proliferating wing cells is distinct from that in the none-dividing eye cells or the ability of activated Ras to induce growth, and that RBF may have a role in regulating growth in the proliferating wing discs [4].
  • Therefore, we have analyzed whether the developmentally controlled inactivation of Cyclin E-Cdk2 required for the epidermal cell proliferation arrest occurs as a consequence of Cyclin D-Cdk4 inactivation [5].

Biological context of Cdk4


Anatomical context of Cdk4

  • Cells homozygous mutant for mRpL12 have reduced mitochondrial activity, and exhibit growth defects that are very similar to those of cdk4 null cells [2].

Other interactions of Cdk4

  • In DROSOPHILA:, single genes for Cyclin D and Cdk4 have been identified, simplifying genetic analysis [3].
  • However, the growth of cells and of the organism is reduced in Cdk4 mutants, indicating a role of D-type cyclin-dependent protein kinases in the modulation of growth rates [3].
  • Epistasis analysis places Hph downstream of CycD/Cdk4 [9].
  • These results demonstrate a new function for Cdk4 and a new mode of STAT activation [8].
  • Specific genetic interactions between Cdk4 and hop mutations suggest that Cdk4 functions downstream of the HOP tyrosine kinase [10].


  1. The Drosophila cyclin D-Cdk4 complex promotes cellular growth. Datar, S.A., Jacobs, H.W., de la Cruz, A.F., Lehner, C.F., Edgar, B.A. EMBO J. (2000) [Pubmed]
  2. The Drosophila mitochondrial ribosomal protein mRpL12 is required for Cyclin D/Cdk4-driven growth. Frei, C., Galloni, M., Hafen, E., Edgar, B.A. EMBO J. (2005) [Pubmed]
  3. Drosophila Cdk4 is required for normal growth and is dispensable for cell cycle progression. Meyer, C.A., Jacobs, H.W., Datar, S.A., Du, W., Edgar, B.A., Lehner, C.F. EMBO J. (2000) [Pubmed]
  4. The role of RBF in developmentally regulated cell proliferation in the eye disc and in Cyclin D/Cdk4 induced cellular growth. Xin, S., Weng, L., Xu, J., Du, W. Development (2002) [Pubmed]
  5. Cyclin D-cdk4 is not a master regulator of cell multiplication in Drosophila embryos. Meyer, C.A., Jacobs, H.W., Lehner, C.F. Curr. Biol. (2002) [Pubmed]
  6. Cyclin D does not provide essential Cdk4-independent functions in Drosophila. Emmerich, J., Meyer, C.A., de la Cruz, A.F., Edgar, B.A., Lehner, C.F. Genetics (2004) [Pubmed]
  7. Cyclin D/Cdk4: new insights from Drosophila. Frei, C. Cell Cycle (2004) [Pubmed]
  8. A new trick for Cyclin-Cdk: activation of STAT. Silver, D.L., Montell, D.J. Dev. Cell (2003) [Pubmed]
  9. Drosophila cyclin D/Cdk4 requires Hif-1 prolyl hydroxylase to drive cell growth. Frei, C., Edgar, B.A. Dev. Cell (2004) [Pubmed]
  10. Cyclin D-Cdk4 and cyclin E-Cdk2 regulate the Jak/STAT signal transduction pathway in Drosophila. Chen, X., Oh, S.W., Zheng, Z., Chen, H.W., Shin, H.H., Hou, S.X. Dev. Cell (2003) [Pubmed]
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