mdm2 expression is induced by wild type p53 activity

EMBO J. 1993 Feb;12(2):461-8.

Abstract

We have recently characterized a 95 kDa protein, p95, which exhibits enhanced binding to temperature-sensitive p53 (ts-p53) when cells are shifted down to 32.5 degrees C, a temperature at which ts-p53 possesses wild-type (wt)-like activities. In the present study we show that p95 is a product of the mdm2 putative proto-oncogene. The enhanced complex formation of mdm2 with ts-p53 in cells maintained at 32.5 degrees C is due to an elevation in total mdm2 protein levels following the temperature shift. We further demonstrate that the induction of mdm2 expression by t p53 activity is at the mRNA level. The induction occurs with very rapid kinetics and does not require de novo protein synthesis, suggesting a direct involvement of p53 in the process. Based on these data and on recent findings implicating p53 as a transcription factor, we suggest that the mdm2 gene is a target for activation by wt p53. In view of the ability of mdm2 to act as a specific antagonist of p53 activity, this induction process may serve to tightly autoregulate p53 activity in living cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Cells, Cultured
  • DNA
  • Gene Expression Regulation*
  • Genes, p53*
  • Molecular Sequence Data
  • Neoplasm Proteins / genetics*
  • Nuclear Proteins*
  • Proto-Oncogene Proteins c-mdm2
  • Proto-Oncogene Proteins*
  • RNA, Messenger / metabolism
  • Rats

Substances

  • Neoplasm Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • DNA
  • Mdm2 protein, rat
  • Proto-Oncogene Proteins c-mdm2