p19ARF targets certain E2F species for degradation

Fabio Martelli, Timothy Hamilton, Daniel P. Silver, Norman E. Sharpless, Nabeel Bardeesy, Mihail Rokas, Ronald A. DePinho, David M. Livingston, Steven R. Grossman

Research output: Contribution to journalArticle

Abstract

p19ARF suppresses the growth of cells lacking p53 through an unknown mechanism. p19ARF was found to complex with transcription factors E2F1, -2, and -3. Levels of endogenous or ectopically expressed E2F1, -2, and -3, but not E2F6, were reduced after synthesis of p19ARF, through a mechanism involving increased turnover, p19ARF-induced degradation of E2F1 depended on a functional proteasome, and E2F1 was relocalized to nucleoli when coexpressed with p19ARF. Consistent with reduced levels of E2F1 and E2F3, the proliferation of cells defective for p53 function was suppressed by p19ARF, and the effect was partially reversed by ectopic overexpression of E2F1. These results suggest a broader role for p19ARF as a tumor suppressor, in which targeting of certain E2F species may cooperate with stimulation of the p53 pathway to counteract oncogenic growth signals.

Original languageEnglish
Pages (from-to)4455-4460
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number8
DOIs
Publication statusPublished - Apr 10 2001

ASJC Scopus subject areas

  • Genetics
  • General

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    Martelli, F., Hamilton, T., Silver, D. P., Sharpless, N. E., Bardeesy, N., Rokas, M., DePinho, R. A., Livingston, D. M., & Grossman, S. R. (2001). p19ARF targets certain E2F species for degradation. Proceedings of the National Academy of Sciences of the United States of America, 98(8), 4455-4460. https://doi.org/10.1073/pnas.081061398