PML is a direct p53 target that modulates p53 effector functions

de Stanchina, E., Querido, E., Narita, M., Davuluri, R. V., Pandolfi, P. P., Ferbeyre, G., Lowe, S. W. (February 2004) PML is a direct p53 target that modulates p53 effector functions. Mol Cell, 13 (4). pp. 523-35. ISSN 1097-2765 (Print)

URL: http://www.sciencedirect.com/science?_ob=ArticleUR...
DOI: 10.1016/S1097-2765(04)00062-0

Abstract

The p53 tumor suppressor promotes cell cycle arrest or apoptosis in response to stress. Previous work suggests that the promyelocytic leukemia gene (PML) can act upstream of p53 to enhance transcription of p53 targets by recruiting p53 to nuclear bodies (NBs). We show that PML is itself a p53 target gene that also acts downstream of p53 to potentiate its antiproliferative effects. Hence, p53 is required for PML induction in response to oncogenes and DNA damaging chemotherapeutics. Furthermore, the PML gene contains p53 binding sites that confer p53 responsiveness to a heterologous reporter and can bind p53 in vitro and in vivo. Finally, cells lacking PML show a reduced propensity to undergo senescence or apoptosis in response to p53 activation, despite the induction of several p53 target genes. These results identify an additional element of PML regulation and establish PML as a mediator of p53 tumor suppressor functions.

Item Type: Paper
Uncontrolled Keywords: Animals Apoptosis genetics Base Sequence Binding Sites Cell Aging genetics Cell Line Cell Survival genetics Fibroblasts cytology Gene Expression Regulation Neoplastic Genes Reporter Genes Tumor Suppressor Genes p53 Genes ras Humans Leukemia Promyelocytic Acute genetics Mice Mice Knockout Neoplasm Proteins genetics Nuclear Proteins Promoter Regions (Genetics) Retroviridae genetics Signal Transduction Transcription Factors genetics Tumor Suppressor Protein p53 metabolism Tumor Suppressor Proteins
Subjects: organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > p53
CSHL Authors:
Communities: CSHL labs > Lowe lab
Depositing User: CSHL Librarian
Date: 27 February 2004
Date Deposited: 09 Feb 2012 16:58
Last Modified: 09 Feb 2012 16:58
URI: http://repository.cshl.edu/id/eprint/22357

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