Cyclin-dependent kinase 4

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Cyclin-dependent kinase 4
Identifiers
Symbol(s) CDK4; CMM3; MGC14458; PSK-J3
External IDs OMIM: 123829 MGI: 88357 Homologene: 55429
RNA expression pattern

More reference expression data

Orthologs
Human Mouse
Entrez 1019 12567
Ensembl ENSG00000135446 na
Uniprot P11802 na
Refseq NM_000075 (mRNA)
NP_000066 (protein) 		NM_009870 (mRNA)
NP_034000 (protein)
Location Chr 12: 56.43 - 56.43 Mb na
Pubmed search [1] [2]

Cyclin-dependent kinase 4 is part of the cyclin-dependent kinase family.


The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is highly similar to the gene products of S. cerevisiae cdc28 and S. pombe cdc2. It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16(INK4a). This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. Multiple polyadenylation sites of this gene have been reported.[1]


It is regulated by Cyclin D.

References

  1. ↑ Entrez Gene: CDK4 cyclin-dependent kinase 4.

Further reading

  • Hanks SK (1987). "Homology probing: identification of cDNA clones encoding members of the protein-serine kinase family.". Proc. Natl. Acad. Sci. U.S.A. 84 (2): 388-92. PMID 2948189.
  • Hall M, Bates S, Peters G (1995). "Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to cyclins.". Oncogene 11 (8): 1581-8. PMID 7478582.
  • Tassan JP, Jaquenoud M, Léopold P, et al. (1995). "Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C.". Proc. Natl. Acad. Sci. U.S.A. 92 (19): 8871-5. PMID 7568034.
  • Mitchell EL, White GR, Santibanez-Koref MF, et al. (1995). "Mapping of gene loci in the Q13-Q15 region of chromosome 12.". Chromosome Res. 3 (4): 261-2. PMID 7606365.
  • Wölfel T, Hauer M, Schneider J, et al. (1995). "A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma.". Science 269 (5228): 1281-4. PMID 7652577.
  • Hirai H, Roussel MF, Kato JY, et al. (1995). "Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6.". Mol. Cell. Biol. 15 (5): 2672-81. PMID 7739547.
  • Chan FK, Zhang J, Cheng L, et al. (1995). "Identification of human and mouse p19, a novel CDK4 and CDK6 inhibitor with homology to p16ink4.". Mol. Cell. Biol. 15 (5): 2682-8. PMID 7739548.
  • Guan KL, Jenkins CW, Li Y, et al. (1995). "Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/MTS2-related CDK6 inhibitor, correlates with wild-type pRb function.". Genes Dev. 8 (24): 2939-52. PMID 8001816.
  • Kato JY, Matsuoka M, Strom DK, Sherr CJ (1994). "Regulation of cyclin D-dependent kinase 4 (cdk4) by cdk4-activating kinase.". Mol. Cell. Biol. 14 (4): 2713-21. PMID 8139570.
  • Khatib ZA, Matsushime H, Valentine M, et al. (1993). "Coamplification of the CDK4 gene with MDM2 and GLI in human sarcomas.". Cancer Res. 53 (22): 5535-41. PMID 8221695.
  • Serrano M, Hannon GJ, Beach D (1994). "A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4.". Nature 366 (6456): 704-7. doi:10.1038/366704a0. PMID 8259215.
  • Demetrick DJ, Zhang H, Beach DH (1994). "Chromosomal mapping of human CDK2, CDK4, and CDK5 cell cycle kinase genes.". Cytogenet. Cell Genet. 66 (1): 72-4. PMID 8275715.
  • Kato J, Matsushime H, Hiebert SW, et al. (1993). "Direct binding of cyclin D to the retinoblastoma gene product (pRb) and pRb phosphorylation by the cyclin D-dependent kinase CDK4.". Genes Dev. 7 (3): 331-42. PMID 8449399.
  • Zuo L, Weger J, Yang Q, et al. (1996). "Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma.". Nat. Genet. 12 (1): 97-9. doi:10.1038/ng0196-97. PMID 8528263.
  • Andersson B, Wentland MA, Ricafrente JY, et al. (1996). "A "double adaptor" method for improved shotgun library construction.". Anal. Biochem. 236 (1): 107-13. doi:10.1006/abio.1996.0138. PMID 8619474.
  • Knudsen ES, Wang JY (1996). "Differential regulation of retinoblastoma protein function by specific Cdk phosphorylation sites.". J. Biol. Chem. 271 (14): 8313-20. PMID 8626527.
  • Poon RY, Jiang W, Toyoshima H, Hunter T (1996). "Cyclin-dependent kinases are inactivated by a combination of p21 and Thr-14/Tyr-15 phosphorylation after UV-induced DNA damage.". J. Biol. Chem. 271 (22): 13283-91. PMID 8662825.
  • Stepanova L, Leng X, Parker SB, Harper JW (1996). "Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4.". Genes Dev. 10 (12): 1491-502. PMID 8666233.
  • Dai K, Kobayashi R, Beach D (1996). "Physical interaction of mammalian CDC37 with CDK4.". J. Biol. Chem. 271 (36): 22030-4. PMID 8703009.
  • Fåhraeus R, Paramio JM, Ball KL, et al. (1996). "Inhibition of pRb phosphorylation and cell-cycle progression by a 20-residue peptide derived from p16CDKN2/INK4A.". Curr. Biol. 6 (1): 84-91. PMID 8805225.

External links

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v • d • e
Cell cycle proteins
CyclinA - B - D - E
Cyclin-dependent kinase2 - 3 - 4 - 5 - 6 - 7 - 8 - 9 - 10 - CDK-activating kinase
Cyclin-dependent kinase inhibitor proteinp14arf/p16INK4a - p21 - p27 - p57
OtherCdc2 - Cdc25 - Cdc42 - Cellular apoptosis susceptibility protein - E2F - Maturation promoting factor - Wee

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Acknowledgement and Attribution Regarding Sources of Content

Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .

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