PML is a direct p53 target that modulates p53 effector functions Journal Article
| Authors: | de Stanchina, E.; Querido, E.; Narita, M.; Davuluri, R. V.; Pandolfi, P. P.; Ferbeyre, G.; Lowe, S. W. |
| Article Title: | PML is a direct p53 target that modulates p53 effector functions |
| 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. |
| Keywords: | signal transduction; controlled study; nonhuman; protein function; animal cell; mouse; animals; mice; mice, knockout; dna damage; cell survival; gene targeting; apoptosis; protein targeting; neoplasm proteins; cell line; genetic transcription; protein p53; animalia; transcription factors; nuclear proteins; oncogene; leukemia, promyelocytic, acute; gene expression regulation, neoplastic; gene identification; tumor suppressor proteins; promyelocytic leukemia; reporter gene; fibroblasts; tumor suppressor protein p53; base sequence; binding sites; genes, reporter; genes, ras; cell aging; genes, tumor suppressor; retroviridae; genes, p53; promyelocytic leukemia protein; promoter regions (genetics); humans; article |
| Journal Title: | Molecular Cell |
| Volume: | 13 |
| Issue: | 4 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2004-02-27 |
| Start Page: | 523 |
| End Page: | 535 |
| Language: | English |
| DOI: | 10.1016/s1097-2765(04)00062-0 |
| PROVIDER: | scopus |
| PUBMED: | 14992722 |
| DOI/URL: | |
| Notes: | Mol. Cell -- Cited By (since 1996):168 -- Export Date: 16 June 2014 -- CODEN: MOCEF -- Source: Scopus |
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