Cell Cycle / Checkpoint Control

The tumor suppressor protein p21 Waf1/Cip1 acts as an inhibitor of cell cycle progression. It functions in stoichiometric relationships forming heterotrimeric complexes with cyclins and cyclin-dependent kinases. In association with CDK2 complexes, it serves to inhibit kinase activity and block progression through G1/S (1). However, p21 may also enhance assembly and activity in complexes of CDK4 or CDK6 and cyclin D (2). The carboxy-terminal region of p21 is sufficient to bind and inhibit PCNA, a subunit of DNA polymerase, and may coordinate DNA replication with cell cycle progression (3). Upon UV damage or during cell cycle stages when cdc2/cyclin B or CDK2/cyclin A is active, p53 is phosphorylated and upregulates p21 transcription via a p53-responsive element (4). Protein levels of p21 are downregulated through ubiquitination and proteasomal degradation (5).

1. Pestell, R.G. et al. (1999) Endocrine Rev. 20, 501-534.
2. Cheng, J. et al. (1999) EMBO J. 18, 1571-1583.
3. Flores-Rozas, H. et al. (1994) Proc. Natl. Acad. Sci. USA 91, 8655-8659.
4. Wang, Y. and Prives, C. (1995) Nature 376, 88-91.
5. Sheaff, R.J. et al. (2000) Cell 5, 403-410.

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p21 Waf1/Cip1 Blocking Peptide

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