Cyclin-dependent kinase 2
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Cyclin-dependent kinase 2 also known as CDK2 is a human gene[1][2]
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[edit] Function
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. 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.[2]
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.[3]
[edit] Inhibitors
Known CDK inhibitors are p21Cip1 (CDKN1A) and p27Kip1 (CDKN1B).[4] Drugs which inhibit Cdk2 and arrest the cell cycle 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.[5]
[edit] Gene regulation
In melanocytic cell types, expression of the CDK2 gene is regulated by the Microphthalmia-associated transcription factor[6][7].
[edit] References
- ^ 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:. PMID 1653904.
- ^ a b "Entrez Gene: CDK2 cyclin-dependent kinase 2". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1017.
- ^ Berthet C, Aleem E, Coppola V, Tessarollo L, Kaldis P (October 2003). "Cdk2 knockout mice are viable". Curr. Biol. 13 (20): 1775–85. doi:. PMID 14561402. http://linkinghub.elsevier.com/retrieve/pii/S0960982203006936.
- ^ Levkau B, Koyama H, Raines EW, Clurman BE, Herren B, Orth K, Roberts JM, Ross R (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:. PMID 9660939.
- ^ Davis ST, Benson BG, Bramson HN, Chapman DE, Dickerson SH, Dold KM, Eberwein DJ, Edelstein M, Frye SV, Gampe Jr RT, Griffin RJ, Harris PA, Hassell AM, Holmes WD, Hunter RN, Knick VB, Lackey K, Lovejoy B, Luzzio MJ, Murray D, Parker P, Rocque WJ, Shewchuk L, Veal JM, Walker DH, Kuyper LF (January 2001). "Prevention of chemotherapy-induced alopecia in rats by CDK inhibitors". Science (journal) 291 (5501): 134–7. doi:. PMID 11141566.
- ^ Du J, Widlund HR, Horstmann MA, 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:. PMID 15607961.
- ^ Hoek KS, Schlegel NC, Eichhoff OM, et al. (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. doi:.
[edit] Further reading
- Kaldis P, Aleem E (2007). "Cell cycle sibling rivalry: Cdc2 vs. Cdk2.". Cell Cycle 4 (11): 1491–4. PMID 16258277.
- Moore NL, Narayanan R, Weigel NL (2007). "Cyclin dependent kinase 2 and the regulation of human progesterone receptor activity.". Steroids 72 (2): 202–9. doi:. PMID 17207508.
[edit] External links
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