Regulation of E2Fs and Senescence by PML Nuclear Bodies

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2011 Jan 6

PMID 21205865

Citations 80

Authors

Mathieu Vernier

Veronique Bourdeau

Marie-France Gaumont-Leclerc

Olga Moiseeva

Virginie Begin

Fred Saad

Anne-Marie Mes-Masson

Gerardo Ferbeyre

Affiliations

Soon will be listed here.

Abstract

The tumor suppressor PML (promyelocytic leukemia protein) regulates cellular senescence and terminal differentiation, two processes that implicate a permanent exit from the cell cycle. Here, we show that the mechanism by which PML induces a permanent cell cycle exit and activates p53 and senescence involves a recruitment of E2F transcription factors bound to their promoters and the retinoblastoma (Rb) proteins to PML nuclear bodies enriched in heterochromatin proteins and protein phosphatase 1α. Blocking the functions of the Rb protein family or adding back E2Fs to PML-expressing cells can rescue their defects in E2F-dependent gene expression and cell proliferation, inhibiting the senescent phenotype. In benign prostatic hyperplasia, a neoplastic disease that displays features of senescence, PML was found to be up-regulated and forming nuclear bodies. In contrast, PML bodies were rarely visualized in prostate cancers. The newly defined PML/Rb/E2F pathway may help to distinguish benign tumors from cancers, and suggest E2F target genes as potential targets to induce senescence in human tumors.

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