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

Oncogene. 2002 Oct 3;21(44):6722-8. doi: 10.1038/sj.onc.1205874.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / chemistry*
  • Codon
  • DNA Damage
  • Female
  • Humans
  • Mice
  • Nuclear Proteins*
  • Protein Isoforms
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-mdm2
  • S Phase
  • Transcriptional Activation
  • Tumor Suppressor Protein p53 / chemistry*
  • Tumor Suppressor Protein p53 / isolation & purification
  • Tumor Suppressor Protein p53 / physiology


  • Codon
  • Nuclear Proteins
  • Protein Isoforms
  • Proto-Oncogene Proteins
  • Tumor Suppressor Protein p53
  • MDM2 protein, human
  • Mdm2 protein, mouse
  • Proto-Oncogene Proteins c-mdm2