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

Fusion of the promyelocytic leukemia (PML) protein to the retinoic acid receptor-α (RARα) 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-RARα blocks these fu...

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Bibliographic Details
Published in:Molecular cell 2001-06, Vol.7 (6), p.1233-1243
Main Authors: Khan, Md Matiullah, Nomura, Teruaki, Kim, Hyungtae, Kaul, Sunil C., Wadhwa, Renu, Shinagawa, Toshie, Ichikawa-Iwata, Emi, Zhong, Sue, Pandolfi, Pier Paolo, Ishii, Shunsuke
Format: Article
Language:English
Subjects:
c-Ski protein
Mad protein
mSin3A protein
N-Cor protein
PML protein
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Summary:Fusion of the promyelocytic leukemia (PML) protein to the retinoic acid receptor-α (RARα) 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-RARα blocks these functions of PML. However, the mechanisms of leukemogenesis by PML-RARα 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-RARα has the two corepressor-interacting sites and inhibits Mad-mediated repression, suggesting that aberrant binding of PML-RARα to the corepressor complexes may lead to abrogation of the corepressor function. These mechanisms may contribute to events leading to leukemogenesis.
ISSN:1097-2765
1097-4164
DOI:10.1016/S1097-2765(01)00257-X