Role of PML and PML-RARα in Mad-Mediated Transcriptional Repression

Autor: Renu Wadhwa, Toshie Shinagawa, Sunil C. Kaul, Matiullah Khan, Teruaki Nomura, Shunsuke Ishii, Sue Zhong, Hyungtae Kim, Emi Ichikawa-Iwata, Pier Paolo Pandolfi
Rok vydání: 2001
Předmět:
Transcriptional Activation
Receptors
Retinoic Acid
viruses
Histone Deacetylase 1
Promyelocytic Leukemia Protein
Biology
Histone Deacetylases
law.invention
Promyelocytic leukemia protein
Leukemia
Promyelocytic
Acute
law
Proto-Oncogene Proteins
Tumor Cells
Cultured
medicine
Animals
Humans
Nuclear Receptor Co-Repressor 1
Luciferases
Molecular Biology
Psychological repression
Mammals
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Gene Expression Regulation
Leukemic
Retinoic Acid Receptor alpha
Tumor Suppressor Proteins
Nuclear Proteins
virus diseases
Cell Biology
medicine.disease
HDAC1
Neoplasm Proteins
DNA-Binding Proteins
Repressor Proteins
Sin3 Histone Deacetylase and Corepressor Complex
Retinoic acid receptor
Leukemia
Lac Operon
Retinoic acid receptor alpha
biology.protein
Cancer research
Suppressor
Corepressor
Transcription Factors
Zdroj: Molecular Cell. 7:1233-1243
ISSN: 1097-2765
DOI: 10.1016/s1097-2765(01)00257-x
Popis: Fusion of the promyelocytic leukemia (PML) protein to the retinoic acid receptor-alpha (RARalpha) generates the transforming protein of acute promyelocytic leukemias. PML appears to be involved in multiple functions, including apoptosis and transcriptional activation by RAR, whereas PML-RARalpha blocks these functions of PML. However, the mechanisms of leukemogenesis by PML-RARalpha remain elusive. Here we show that PML interacts with multiple corepressors (c-Ski, N-CoR, and mSin3A) and histone deacetylase 1, and that this interaction is required for transcriptional repression mediated by the tumor suppressor Mad. PML-RARalpha has the two corepressor-interacting sites and inhibits Mad-mediated repression, suggesting that aberrant binding of PML-RARalpha to the corepressor complexes may lead to abrogation of the corepressor function. These mechanisms may contribute to events leading to leukemogenesis.
Databáze: OpenAIRE
Externí odkaz: