Role of PML and PML-RARα in Mad-mediated transcriptional repression

被引：123

作者：

Khan, MM

Nomura, T

Kim, H

Kaul, SC

Wadhwa, R

Shinagawa, T

Ichikawa-Iwata, E

Zhong, S

Pandolfi, PP

Ishii, S ^{[1
]}

机构：

[1] Cornell Univ, Grad Sch Med Sci, Dept Human Genet,Sloan Kettering Div, Mol Biol Program,Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA

[2] RIKEN, Tsukuba Inst, Genet Mol Lab, Tsukuba, Ibaraki 3050074, Japan

[3] JST, CREST, Res Project, Tsukuba, Ibaraki 3050074, Japan

[4] Natl Inst Biosci & Human Technol, Agcy Ind Sci & Technol, Tsukuba, Ibaraki 3050046, Japan

[5] Chugai Res Inst Mol Med, Ibaraki, Osaka 3004101, Japan

来源：

MOLECULAR CELL | 2001年 / 7卷 / 06期

关键词：

D O I：

10.1016/S1097-2765(01)00257-X

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Fusion of the promyelocytic leukemia (PML) protein to the retinoic acid receptor-alpha (RAR alpha) 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-RAR alpha blocks these functions of PML. However, the mechanisms of leukemogenesis by PML-RAR alpha 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-RAR alpha has the two corepressor-interacting sites and inhibits Mad-mediated repression, suggesting that aberrant binding of PML-RAR alpha to the corepressor complexes may lead to abrogation of the corepressor function. These mechanisms may contribute to events leading to leukemogenesis.

引用

页码：1233 / 1243

页数：11

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