BACKGROUND p21WAF1/Cip1 belongs to the Cip/Kip family of cyclinkinase inhibitors (CKI) (p21Waf1/Cip1, p27Kip1, p57Kip1). p21Waf1/Cip1 was first described as a potent and universal inhibitor of cyclin-dependent kinases (Cdks). Two forms of functionally active p21 has been localized and described: a nuclear and acytoplasmic forms. p21 functions as a checkpoint in the cell cycle by inhibiting cdks at the G1/S and G2/M interfaces.1 p21 has been shown to bind to cyclin-cdk complexes, preventing phosphorylation of the retinoblastoma protein. When this happens, the E2F pathway is blocked and the cell cycle is arrested at the G1/S interface.
p21 expression is usually controlled at the transcriptional level by either the p53-dependent or -independent pathway,2 but p21 expression can also be regulated at the post-transcriptional level. Short wavelength UVC was found to induce p21 in a p53-dependent fashion by post-transcriptional modifications that led to enhanced stability of p21 mRNA.3 The transcription factors C/EBPa and C/EBPb were found to interact with p21 protein and protect it from proteolytic degradation. In a number of other cell lines, post-transcriptional events strongly influence p21 expression following genotoxic stress. Stress activated kinases p38alpha and JNK 1 were shown to stabilize p21 by phosphorylation at serine 130. p21 was shown to promote apoptosis, protect cells from undergoing apoptosis, inhibit or promote differentiation.4
1. Harper, J.W. et al: Cell 75:805-816, 1993
2. Blundell, R.A.:Am. J. Biochem. Biotech. 2:33-40, 2006
3. Wang, W. et al: Mol. Cell. Biol. 20:760-771, 2000
4. Cox, L. S.: J. Path. 183:134-140, 1999
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