Cyclin-dependent kinase 4

Cyclin-dependent kinase 4
Cyclin-dependent kinase 4

Rendering based on PDB 1LD2.
Symbols CDK4; CMM3; MGC14458; PSK-J3
External IDs OMIM123829 MGI88357 HomoloGene55429 GeneCards: CDK4 Gene
EC number
RNA expression pattern
PBB GE CDK4 202246 s at tn.png
More reference expression data
Species Human Mouse
Entrez 1019 12567
Ensembl ENSG00000135446 n/a
UniProt P11802 n/a
RefSeq (mRNA) NM_000075.2 NM_009870.3
RefSeq (protein) NP_000066.1 NP_034000.1
Location (UCSC) Chr 12:
58.14 – 58.15 Mb
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.



Cyclin-dependent kinase 4 has been shown to interact with SERTAD1,[2][3] CDC37,[4][5][6][7] CEBPA,[8] PCNA,[9][10] Cyclin D3,[11][12][13][14] Cyclin D1,[3][9][13][15][16][17] CDKN2C,[4][18] MyoD,[19][20] P16,[2][3][4][9][17][21] CDKN2B,[11][22] Drebrin-like[4] and CDKN1B.[13][16]

Overview of signal transduction pathways involved in apoptosis.


  1. ^ "Entrez Gene: CDK4 cyclin-dependent kinase 4". 
  2. ^ a b Li, Junan, , Tsai Ming-Daw, Muscarella Peter, Tsai, Ming-Daw, Muscarella, Peter (Apr. 2004). "The nuclear protein p34SEI-1 regulates the kinase activity of cyclin-dependent kinase 4 in a concentration-dependent manner". Biochemistry (United States) 43 (14): 4394–9. doi:10.1021/bi035601s. ISSN 0006-2960. PMID 15065884. 
  3. ^ a b c Sugimoto, M, Ohtani N, Hampson L, Hampson I N, Shimamoto A, Furuichi Y, Okumura K, Niwa S et al. (Nov. 1999). "Regulation of CDK4 activity by a novel CDK4-binding protein, p34SEI-1". Genes Dev. (UNITED STATES) 13 (22): 3027–33. doi:10.1101/gad.13.22.3027. ISSN 0890-9369. PMC 317153. PMID 10580009. 
  4. ^ a b c d Ewing, Rob M, Elisma Fred, Li Hongyan, Taylor Paul, Climie Shane, McBroom-Cerajewski Linda, Robinson Mark D, Connor Liam et al. (2007). "Large-scale mapping of human protein–protein interactions by mass spectrometry". Mol. Syst. Biol. (England) 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931. 
  5. ^ Dai, K, , Beach D, Beach, D (Sep. 1996). "Physical interaction of mammalian CDC37 with CDK4". J. Biol. Chem. (UNITED STATES) 271 (36): 22030–4. doi:10.1074/jbc.271.36.22030. ISSN 0021-9258. PMID 8703009. 
  6. ^ Lamphere, L, Xu X, Brizuela L, Keezer S, Sardet C, Draetta G F, , Gyuris J, Gyuris, Jeno (Apr. 1997). "Interaction between Cdc37 and Cdk4 in human cells". Oncogene (ENGLAND) 14 (16): 1999–2004. doi:10.1038/sj.onc.1201036. ISSN 0950-9232. PMID 9150368. 
  7. ^ Stepanova, L, Parker S B, , Harper J W, Harper, J W (Jun. 1996). "Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4". Genes Dev. (UNITED STATES) 10 (12): 1491–502. doi:10.1101/gad.10.12.1491. ISSN 0890-9369. PMID 8666233. 
  8. ^ Wang, H, Wilde M, Welm A, Goode T, Roesler W J, , Timchenko N A, Timchenko, Nikolai A (Oct. 2001). "C/EBPalpha arrests cell proliferation through direct inhibition of Cdk2 and Cdk4". Mol. Cell (United States) 8 (4): 817–28. doi:10.1016/S1097-2765(01)00366-5. ISSN 1097-2765. PMID 11684017. 
  9. ^ a b c Serrano, M, , Beach D, Beach, David (Dec. 1993). "A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4". Nature (ENGLAND) 366 (6456): 704–7. doi:10.1038/366704a0. ISSN 0028-0836. PMID 8259215. 
  10. ^ Xiong, Y, , Beach D, Beach, D (Aug. 1993). "Subunit rearrangement of the cyclin-dependent kinases is associated with cellular transformation". Genes Dev. (UNITED STATES) 7 (8): 1572–83. doi:10.1101/gad.7.8.1572. ISSN 0890-9369. PMID 8101826. 
  11. ^ a b Rual, Jean-François, Hao Tong, Hirozane-Kishikawa Tomoko, Dricot Amélie, Li Ning, Berriz Gabriel F, Gibbons Francis D, Dreze Matija et al. (Oct. 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature (England) 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514. 
  12. ^ Arsenijevic, Tatjana, Dumont Jacques E, Roger Pierre P, , Pirson Isabelle, Pirson, Isabelle (Mar. 2004). "A novel partner for D-type cyclins: protein kinase A-anchoring protein AKAP95". Biochem. J. (England) 378 (Pt 2): 673–9. doi:10.1042/BJ20031765. PMC 1223988. PMID 14641107. 
  13. ^ a b c Lin, J, , Okayama H, Okayama, Hiroto (Apr. 2001). "Cdk6-cyclin D3 complex evades inhibition by inhibitor proteins and uniquely controls cell's proliferation competence". Oncogene (England) 20 (16): 2000–9. doi:10.1038/sj.onc.1204375. ISSN 0950-9232. PMID 11360184. 
  14. ^ Zhang, Q, , Wolgemuth D J, Wolgemuth, DJ (Jun. 1999). "Developmentally regulated expression of cyclin D3 and its potential in vivo interacting proteins during murine gametogenesis". Endocrinology (UNITED STATES) 140 (6): 2790–800. doi:10.1210/en.140.6.2790. ISSN 0013-7227. PMID 10342870. 
  15. ^ Taulés, M, Talaya D, López-Girona A, Bachs O, , Agell N, Agell, N (Dec. 1998). "Calmodulin is essential for cyclin-dependent kinase 4 (Cdk4) activity and nuclear accumulation of cyclin D1-Cdk4 during G1". J. Biol. Chem. (UNITED STATES) 273 (50): 33279–86. doi:10.1074/jbc.273.50.33279. ISSN 0021-9258. PMID 9837900. 
  16. ^ a b Cariou, S, Flanagan W M, Milic A, Bhattacharya N, , Slingerland J M, Slingerland, JM (Aug. 2000). "Down-regulation of p21WAF1/CIP1 or p27Kip1 abrogates antiestrogen-mediated cell cycle arrest in human breast cancer cells". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 97 (16): 9042–6. doi:10.1073/pnas.160016897. ISSN 0027-8424. PMC 16818. PMID 10908655. 
  17. ^ a b Coleman, K G, Morrissey D, Mulheron J, Sedman S A, Brinkley P, Price S, , Webster K R, Webster, KR (Jul. 1997). "Identification of CDK4 sequences involved in cyclin D1 and p16 binding". J. Biol. Chem. (UNITED STATES) 272 (30): 18869–74. doi:10.1074/jbc.272.30.18869. ISSN 0021-9258. PMID 9228064. 
  18. ^ Guan, K L, Li Y, Nichols M A, Wu X, Keefe C L, Matera A G, , O' Xiong Y, Xiong, Y (Dec. 1994). "Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/MTS2-related CDK6 inhibitor, correlates with wild-type pRb function". Genes Dev. (UNITED STATES) 8 (24): 2939–52. doi:10.1101/gad.8.24.2939. ISSN 0890-9369. PMID 8001816. 
  19. ^ Zhang, J M, Wei Q, , Paterson B M, Paterson, BM (Dec. 1999). "Direct inhibition of G(1) cdk kinase activity by MyoD promotes myoblast cell cycle withdrawal and terminal differentiation". EMBO J. (ENGLAND) 18 (24): 6983–93. doi:10.1093/emboj/18.24.6983. ISSN 0261-4189. PMC 1171761. PMID 10601020. 
  20. ^ Zhang, J M, Zhao X, , Paterson B M, Paterson, Bruce M. (Feb. 1999). "Coupling of the cell cycle and myogenesis through the cyclin D1-dependent interaction of MyoD with cdk4". EMBO J. (ENGLAND) 18 (4): 926–33. doi:10.1093/emboj/18.4.926. ISSN 0261-4189. PMC 1171185. PMID 10022835. 
  21. ^ Fåhraeus, R, Ball K L, Laín S, , Lane D P, Lane, David P. (Jan. 1996). "Inhibition of pRb phosphorylation and cell-cycle progression by a 20-residue peptide derived from p16CDKN2/INK4A". Curr. Biol. (ENGLAND) 6 (1): 84–91. doi:10.1016/S0960-9822(02)00425-6. ISSN 0960-9822. PMID 8805225. 
  22. ^ Stelzl, Ulrich, Lalowski Maciej, Haenig Christian, Brembeck Felix H, Goehler Heike, Stroedicke Martin, Zenkner Martina, Schoenherr Anke et al. (Sep. 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell (United States) 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. ISSN 0092-8674. PMID 16169070. 

Further reading

External links

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