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.
Delta N-p53, a natural isoform of p53 lacking the first transactivation domain, counteracts growth suppression by wild-type p53
Courtois, S.; Verhaegh, G.; North, S.; Luciani, M. G.; Lassus, P.; Hibner, U.; Oren, M.; Hainaut, P.
2002-10-03 / vol 21 / pages 6722-6728
in-vitro; mdm2; p53; protein; identification; translation; cell cycle; DNA-binding; delta n-p53; functional domain; initiation; n-terminal domain; p53 isoforms; p63; proteolytic cleavage