Promyelocytic leukemia protein is required for gain of function by mutant p53

Sue Haupt, Silvia Di Agostino, Inbal Mizrahi, Osnat Alsheich-Bartok, Mathijs Voorhoeve, Alex Damalas, Giovanni Blandino, Ygal Haupt

Research output: Contribution to journalArticlepeer-review

Abstract

Mutations in the p53 tumor suppressor are the most common genetic events in human cancer. These mutations not only result in a loss of wild-type p53 activity, but can also lead to a gain of new oncogenic properties. Understanding how these gained functions are regulated is in its infancy. In this study, we show that the promyelocytic leukemia (PML) protein is an important regulator of mutant p53. We show that PML interacts with mutant p53. Importantly, PML enhances the transcriptional activity of mutant p53. Unexpectedly, PML is required for the proliferation and colony formation of cancer cells bearing mutant p53. Down-regulation of PML expression inhibits the growth of mutant p53-expressing cancer cells, predominantly by promoting cell cycle arrest. Our results suggest that the tumor suppression function of PML depends on the status of p53. In the context of mutant p53, PML enhances its cancer-promoting activities.

Original languageEnglish
Pages (from-to)4818-4826
Number of pages9
JournalCancer Research
Volume69
Issue number11
DOIs
Publication statusPublished - Jun 1 2009

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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