Cyclin-dependent kinase 2

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Cyclin-dependent kinase 2
Protein CDK2 PDB 1aq1.png
PDB rendering based on 1aq1[1].
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols CDK2 ; CDKN2; p33(CDK2)
External IDs OMIM116953 MGI104772 HomoloGene74409 ChEMBL: 301 GeneCards: CDK2 Gene
EC number 2.7.11.22
RNA expression pattern
PBB GE CDK2 204252 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1017 12566
Ensembl ENSG00000123374 ENSMUSG00000025358
UniProt P24941 P97377
RefSeq (mRNA) NM_001290230 NM_016756
RefSeq (protein) NP_001277159 NP_058036
Location (UCSC) Chr 12:
56.36 – 56.37 Mb
Chr 10:
128.7 – 128.71 Mb
PubMed search [1] [2]

Cyclin-dependent kinase 2, also known as cell division protein kinase 2, is an enzyme that in humans is encoded by the CDK2 gene.[2][3]

Function[edit]

The protein encoded by this gene is a member of the cyclin-dependent kinase family of Ser/Thr protein kinases. This protein kinase is highly similar to the gene products of S. cerevisiae cdc28, and S. pombe cdc2, also known as Cdk1 in humans. It is a catalytic subunit of the cyclin-dependent kinase complex, whose activity is restricted to the G1-S phase of the cell cycle, and is essential for the G1/S transition. This protein associates with and is regulated by the regulatory subunits of the complex including cyclin E or A. Cyclin E binds G1 phase Cdk2, which is required for the transition from G1 to S phase while binding with Cyclin A is required to progress through the S phase. Its activity is also regulated by phosphorylation. Two alternatively spliced variants and multiple transcription initiation sites of this gene have been reported.[3]

The role of this protein in G1-S transition has been recently questioned as cells lacking Cdk2 are reported to have no problem during this transition.[4]

Inhibitors[edit]

Known CDK inhibitors are p21Cip1 (CDKN1A) and p27Kip1 (CDKN1B).[5] Drugs that inhibit Cdk2 and arrest the cell cycle, such as GW8510 and the experimental cancer drug seliciclib, may reduce the sensitivity of the epithelium to many cell cycle-active antitumor agents and, therefore, represent a strategy for prevention of chemotherapy-induced alopecia.[6]

Gene regulation[edit]

In melanocytic cell types, expression of the CDK2 gene is regulated by the Microphthalmia-associated transcription factor.[7][8]

Interactions[edit]

Cyclin-dependent kinase 2 has been shown to interact with:

Overview of signal transduction pathways involved in apoptosis.

References[edit]

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  2. ^ Tsai LH, Harlow E, Meyerson M (September 1991). "Isolation of the human cdk2 gene that encodes the cyclin A- and adenovirus E1A-associated p33 kinase". Nature 353 (6340): 174–7. doi:10.1038/353174a0. PMID 1653904. 
  3. ^ a b "Entrez Gene: CDK2 cyclin-dependent kinase 2". 
  4. ^ Berthet C, Aleem E, Coppola V, Tessarollo L, Kaldis P (October 2003). "Cdk2 knockout mice are viable". Curr. Biol. 13 (20): 1775–85. doi:10.1016/j.cub.2003.09.024. PMID 14561402. 
  5. ^ Levkau B, Koyama H, Raines EW, Clurman BE, Herren B, Orth K et al. (March 1998). "Cleavage of p21Cip1/Waf1 and p27Kip1 mediates apoptosis in endothelial cells through activation of Cdk2: role of a caspase cascade". Mol. Cell 1 (4): 553–63. doi:10.1016/S1097-2765(00)80055-6. PMID 9660939. 
  6. ^ Davis ST, Benson BG, Bramson HN, Chapman DE, Dickerson SH, Dold KM et al. (January 2001). "Prevention of chemotherapy-induced alopecia in rats by CDK inhibitors". Science 291 (5501): 134–7. doi:10.1126/science.291.5501.134. PMID 11141566.  (Retracted. If this is intentional, please replace {{Retracted}} with {{Retracted|intentional=yes}}.)
  7. ^ Du J, Widlund HR, Horstmann MA, Ramaswamy S, Ross K, Huber WE et al. (2004). "Critical role of CDK2 for melanoma growth linked to its melanocyte-specific transcriptional regulation by MITF". Cancer Cell 6 (6): 565–76. doi:10.1016/j.ccr.2004.10.014. PMID 15607961. 
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  33. ^ a b Yam CH, Ng RW, Siu WY, Lau AW, Poon RY (January 1999). "Regulation of cyclin A-Cdk2 by SCF component Skp1 and F-box protein Skp2". Mol. Cell. Biol. 19 (1): 635–45. PMC 83921. PMID 9858587. 
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Further reading[edit]

External links[edit]