PML-RARα alleviates the transcriptional repression mediated by tumor suppressor Rb Journal Article
| Authors: | Khan, M. Md; Nomura, T.; Kim, H.; Kaul, S. C.; Wadhwa, R.; Zhong, S.; Pandolfi, P. P.; Ishii, S. |
| Article Title: | PML-RARα alleviates the transcriptional repression mediated by tumor suppressor Rb |
| Abstract: | A fusion between the promyelocytic leukemia (PML) protein and the retinoic acid receptor-α (RARα) results in the transforming protein of acute promyelocytic leukemia, PML-RARα. PML has growth-suppressive properties and is localized within distinct nuclear structures referred to as nuclear bodies. PML participates in numerous cellular functions, including transcriptional activation, apoptosis, and transcriptional repression, whereas PML-RARα blocks these functions. However, the role played by PML-RARα in leukemogenesis remains unclear. Here we report that PML is required for transcriptional repression mediated by the tumor suppressor Rb. Rb interacts with the histone decaetylase (HDAC) complex containing co-repressors and represses the transcription of the E2F target genes. Overexpression of PML enhanced Rb-mediated repression. The degree of Rb-mediated repression was weakened by injecting anti-PML antibodies and was lower in Pml-deficient mouse embryonic fibroblasts. PML-RARα inhibited Rb-mediated repression, and two co-repressor-interacting sites on the PML-RARα molecule were required for this activity. Furthermore, PML-RARα blocked the interaction between Rb and HDAC. Thus, aberrant binding of PML-RARα to co-repressor-HDAC complexes may inhibit their association with Rb, resulting in the abrogation of Rb activity. Thus, the disruption of Rb-mediated repression may be a contributory factor in leukemogenesis. |
| Keywords: | dna binding protein; oncoprotein; genetics; dna-binding proteins; nonhuman; protein localization; proteins; cell cycle protein; animal cell; mouse; animal; metabolism; animals; cell cycle proteins; mice; gene targeting; complex formation; gene overexpression; apoptosis; genes; protein protein interaction; neoplasm proteins; cell line; protein binding; gene product; transcription factor; genetic transcription; transcription, genetic; physiology; animalia; transcription factors; tumor suppressor gene; transcription regulation; hybrid protein; tumors; gene disruption; genetic susceptibility; transcription factor e2f; leukemogenesis; tumor protein; promyelocytic leukemia; oncogene proteins, fusion; fibroblast; retinoblastoma protein; thyroid hormone receptor; histone deacetylases; histone deacetylase; zinc finger motif; retinoic acid receptor alpha; e2f transcription factors; priority journal; article; nuclear structures; promyelocytic leukemia retinoic acid receptor alpha fusion oncoprotein; promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 276 |
| Issue: | 47 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2001-11-23 |
| Start Page: | 43491 |
| End Page: | 43494 |
| Language: | English |
| DOI: | 10.1074/jbc.C100532200 |
| PUBMED: | 11583987 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
