DeltaN-p53, a natural isoform of p53 lacking the first transactivation domain, counteracts growth suppression by wild-type p53.
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.
D000818:Animals; D001943:Breast Neoplasms / Q000737:chemistry*; D003062:Codon; D004249:DNA Damage; D005260:Female; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D016196:S Phase; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000302:isolation & purification / Q000502:physiology
D003062:Codon; D009687:Nuclear Proteins; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2