p53 regulation by post-translational modification and nuclear retention in response to diverse stresses

Gretchen S. Jimenez, Shireen H. Khan, Jayne M. Stommel, Geoffrey M. Wahl

Research output: Contribution to journalReview articlepeer-review

162 Scopus citations

Abstract

p53 activation by diverse stresses involves post-translational modifications that alter its structure and result in its nuclear accumulation. We will discuss several unresolved topics regarding p53 regulation which are currently under investigation. DNA damage is perhaps the best-studied stress which activates p53, and recent data implicate phosphorylation at N-terminal serine residues as critical in this process. We discuss recent data regarding the potential kinases which modify p53 and the possible role of the resulting phosphorylation events. By contrast, much less is understood about agents which disrupt the mitotic spindle. The cell cycle phase, induction signal, and biochemical mechanism of the reversible arrest induced by microtubule disruption are currently under investigation. Finally, a keg event in response to any genotoxic stress is the accumulation of p53 in the nucleus. The factors which determine the steady state level of p53 are starting to be elucidated, but the mechanisms responsible for nuclear accumulation and nuclear export remain controversial. We discuss new studies revealing a mechanism for nuclear retention of p53, and the potential contributions of MDM2 to this process.

Original languageEnglish (US)
Pages (from-to)7656-7665
Number of pages10
JournalOncogene
Volume18
Issue number53
DOIs
StatePublished - Dec 13 1999
Externally publishedYes

Keywords

  • DNA damage
  • Microtubule depolymerization
  • Nuclear export signal
  • p53
  • Post translational modification

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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