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Nat Genet. 2006 Oct;38(10):1133-41. Epub 2006 Sep 10.

iASPP preferentially binds p53 proline-rich region and modulates apoptotic function of codon 72-polymorphic p53.

Author information

1
Ludwig Institute for Cancer Research, University College London, 91 Riding House Street, London W1W 7BS, UK.

Abstract

iASPP is one of the most evolutionarily conserved inhibitors of p53, whereas ASPP1 and ASPP2 are activators of p53. We show here that, in addition to the DNA-binding domain, the ASPP family members also bind to the proline-rich region of p53, which contains the most common p53 polymorphism at codon 72. Furthermore, the ASPP family members, particularly iASPP, bind to and regulate the activity of p53Pro72 more efficiently than that of p53Arg72. Hence, escape from negative regulation by iASPP is a newly identified mechanism by which p53Arg72 activates apoptosis more efficiently than p53Pro72.

PMID:
16964264
DOI:
10.1038/ng1879
[Indexed for MEDLINE]

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