PML-RARα Alleviates the Transcriptional Repression Mediated by Tumor Suppressor Rb
| Autor: | Teruaki Nomura, Hyungtae Kim, Shunsuke Ishii, Sue Zhong, Renu Wadhwa, Sunil C. Kaul, Pier Paolo Pandolfi, Matiullah Khan |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Acute promyelocytic leukemia
Oncogene Proteins Fusion Transcription Genetic viruses Cell Cycle Proteins Biology Retinoblastoma Protein Biochemistry Histone Deacetylases Cell Line law.invention Mice Promyelocytic leukemia protein law Transcription (biology) medicine Animals E2F Molecular Biology Psychological repression virus diseases Cell Biology medicine.disease Molecular biology E2F Transcription Factors Neoplasm Proteins Cell biology DNA-Binding Proteins Retinoic acid receptor Histone biology.protein Suppressor Protein Binding Transcription Factors |
| Zdroj: | Journal of Biological Chemistry. 276:43491-43494 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.c100532200 |
| Popis: | A fusion between the promyelocytic leukemia (PML) protein and the retinoic acid receptor-alpha (RARalpha) results in the transforming protein of acute promyelocytic leukemia, PML-RARalpha. 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-RARalpha blocks these functions. However, the role played by PML-RARalpha 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-RARalpha inhibited Rb-mediated repression, and two co-repressor-interacting sites on the PML-RARalpha molecule were required for this activity. Furthermore, PML-RARalpha blocked the interaction between Rb and HDAC. Thus, aberrant binding of PML-RARalpha 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. |
| Databáze: | OpenAIRE |
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