Delta N-p53, a natural isoform of p53 lacking the first transactivation domain, counteracts growth suppression by wild-type p53 - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Oncogene Année : 2002

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

Résumé

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.

Dates et versions

hal-02197521 , version 1 (30-07-2019)

Identifiants

Citer

S. Courtois, G. Verhaegh, S. North, M. G. Luciani, Patrice Lassus, et al.. Delta N-p53, a natural isoform of p53 lacking the first transactivation domain, counteracts growth suppression by wild-type p53. Oncogene, 2002, 21 (44), pp.6722--6728. ⟨10.1038/sj.onc.1205874⟩. ⟨hal-02197521⟩
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