PML is induced by oncogenic ras and promotes premature senescence

Ferbeyre, G., de Stanchina, E., Querido, E., Baptiste, N., Prives, C., Lowe, S. W. (August 2000) PML is induced by oncogenic ras and promotes premature senescence. Genes & Development, 14 (16). pp. 2015-2027. ISSN 0890-9369

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URL: http://www.ncbi.nlm.nih.gov/pubmed/10950866
DOI: 10.1101/gad.14.16.2015

Abstract

Oncogenic ras provokes a senescent-like arrest in human diploid fibroblasts involving the Rb and p53 tumor suppressor pathways. To further characterize this response, we compared gene expression patterns between ras-arrested and quiescent IMR90 fibroblasts. One of the genes up-regulated during ras-induced arrest was promyelocytic leukemia (PML) protein, a potential tumor suppressor that encodes a component of nuclear structures known as promyelocytic oncogenic domains (PODs). PML levels increased during both ras-induced arrest and replicative senescence, leading to a dramatic increase in the size and number of PODs. Forced PML expression was sufficient to promote premature senescence. Like oncogenic ras, PML increased the levels of p16, hypophosphorylated Rb, phosphoserine-15 p53, and expression of p53 transcriptional targets. The fraction of Rb and p53 that colocalized with PML markedly increased during ras-induced arrest, and expression of PML alone forced p53 to the PODs. E1A abolished PML-induced arrest and prevented PML induction and p53 phosphorylation in response to oncogenic ras. These results imply that PML acts with Rb and p53 to promote ras-induced senescence and provide new insights into PML regulation and activity.

Item Type: Paper
Uncontrolled Keywords: senescence ras PML p53 retinoblastoma protein p16 ACUTE PROMYELOCYTIC LEUKEMIA TRANSCRIPTION FACTOR IRF-1 HUMAN-DIPLOID FIBROBLASTS CREB BINDING-PROTEIN HUMAN TUMOR-CELLS REPLICATIVE SENESCENCE P53-DEPENDENT APOPTOSIS ANTICANCER AGENTS NUCLEAR-BODIES MESSENGER-RNA
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > oncogene
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > G protein > Ras
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > senescence
CSHL Authors:
Communities: CSHL labs > Lowe lab
Depositing User: Matt Covey
Date: August 2000
Date Deposited: 30 Jan 2014 15:28
Last Modified: 30 Jan 2014 15:28
PMCID: PMC316863
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29430

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