Aberrant association of promyelocytic leukemia protein-retinoic acid receptor-α with coactivators contributes to its ability to regulate gene expression

Erin L. Reineke, Heng Liu, Minh Lam, Yu Liu, Hung Ying Kao

研究成果: Article同行評審

9 引文 斯高帕斯(Scopus)

摘要

The aberrant association of promyelocytic leukemia protein-retinoic acid receptor-α (PML-RARα) with corepressor complexes is generally thought to contribute to the ability of PML-RARα to regulate transcription. We report here that PML-RARα acquires aberrant association with coactivators. We show that endogenous PML-RARα interacts with the histone acetyltransferases CBP, p300, and SRC-1 in a hormone-independent manner, an association not seen for RARα. This hormone-independent coactivator binding activity requires an intact ligand-binding domain and the NR box of the coactivators. Confocal microscopy studies demonstrate that exogenous PML-RARα sequesters and colocalizes with coactivators. These observations correlate with the ability of PML-RARα to attenuate the transcription activation of the Notch signaling downstream effector, CBF1, and of the glucocorticoid receptor. This includes attenuation of the glucocorticoid-induced leucine zipper (GILZ) and FLJ25390 target genes of the endogenous glucocorticoid receptor. Furthermore, treatment of NB4 cells with all-trans-retinoic acid, which promotes PML-RARα degradation, resulted in increased activation of GILZ. On the basis of these findings, we propose a model in which the hormone-independent association between PML-RARα and coactivators contributes to its ability to regulate gene expression.

原文English
頁(從 - 到)18584-18596
頁數13
期刊Journal of Biological Chemistry
282
發行號25
DOIs
出版狀態Published - 2007 六月 22

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

指紋 深入研究「Aberrant association of promyelocytic leukemia protein-retinoic acid receptor-α with coactivators contributes to its ability to regulate gene expression」主題。共同形成了獨特的指紋。

引用此