DeltaN-p53, a natural isoform of p53 lacking the first transactivation domain, counteracts growth suppression by wild-type p53 - PubMed (original) (raw)

. 2002 Oct 3;21(44):6722-8.

doi: 10.1038/sj.onc.1205874.

Affiliations

• PMID: 12360399
• DOI: 10.1038/sj.onc.1205874

DeltaN-p53, a natural isoform of p53 lacking the first transactivation domain, counteracts growth suppression by wild-type p53

Stéphanie Courtois et al. Oncogene. 2002.

Abstract

The tumor suppressor protein p53 is ubiquitously expressed as a major isoform of 53 kD, but several forms of lower molecular weight have been observed. Here, we describe a new isoform, DeltaN-p53, produced by internal initiation of translation at codon 40 and lacking the N-terminal first transactivation domain. This isoform has impaired transcriptional activation capacity, and does not complex with the p53 regulatory protein Mdm2. Furthermore, DeltaN-p53 oligomerizes with full-length p53 (FL-p53) and negatively regulates its transcriptional and growth-suppressive activities. Consistent with the lack of Mdm2 binding, DeltaN-p53 does not accumulate in response to DNA-damage, suggesting that this isoform is not involved in the response to genotoxic stress. However, in serum-starved cells expressing wild-type p53, DeltaN-p53 becomes the predominant p53 form during the synchronous progression into S phase after serum stimulation. These results suggest that DeltaN-p53 may play a role as a transient, negative regulator of p53 during cell cycle progression.

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