Bag-1M inhibits the transactivation of the glucocorticoid receptor via recruitment of corepressors

Hong, Wei; Baniahmad, Aria; Li, Juan; Chang, Chenglin; Gao, Weizhen; Liu, Yunde

doi:10.1016/j.febslet.2009.07.010

« Previous Next »FEBS Letters
Volume 583, Issue 15 , Pages 2451-2456, 6 August 2009

Bag-1M inhibits the transactivation of the glucocorticoid receptor via recruitment of corepressors

Edited by Robert Barouki

Wei Hong
- Department of Laboratory Medicine, Tianjin Medical University, 300203 Tianjin, China
- Corresponding authors. Fax: +86 22 60357712 (W. Hong), +49 3641 935502 (A. Baniahmad).
Aria Baniahmad
- Institute for Human Genetics and Anthropology, Jena University Hospital, 07740 Jena, Germany
- Corresponding authors. Fax: +86 22 60357712 (W. Hong), +49 3641 935502 (A. Baniahmad).
Juan Li
- Department of Laboratory Medicine, Tianjin Medical University, 300203 Tianjin, China
Chenglin Chang
- Department of Laboratory Medicine, Tianjin Medical University, 300203 Tianjin, China
Weizhen Gao
- Department of Laboratory Medicine, Tianjin Medical University, 300203 Tianjin, China
Yunde Liu
- Department of Laboratory Medicine, Tianjin Medical University, 300203 Tianjin, China

Received 29 April 2009; received in revised form 16 June 2009; accepted 2 July 2009. published online 13 July 2009.

Abstract

The Bcl-2 associated athanogene 1M (Bag-1M) is known to repress the transactivation of the glucocorticoid receptor (GR). We report here that Bag-1M inhibits the action of GR via recruitment of corepressors, including nuclear receptor corepressor (NcoR) and silencing mediator for retinoic acid and thyroid hormone receptor (SMRT), and histone deacetylase (HDAC)3 to the genomic response element of a glucocorticoid-regulated human metallothionein IIa (hMTIIa) gene. A mutant GR lacking the interaction with BAG-1M fails to recruit the corepressors NcoR and SMRT. RNAi-mediated knock down of corepressors and the use of HDAC inhibitor relieved Bag-1M-induced repression on the transactivation of the GR. In addition, Bag-1M is not involved in the degradation of the receptor. These findings indicate a novel mechanism by which Bag-1M acts as a corepressor and downregulates the activity of the GR.

Structured summary

MINT-7216164: HDAC3 (uniprotkb:O15379) physically interacts (MI:0914) with Bag1 (uniprotkb:Q99933) by anti bait coimmunoprecipitation (MI:0006)

MINT-7216183: NCOR (uniprotkb:O75376) physically interacts (MI:0914) with Bag1 (uniprotkb:Q99933) by anti bait coimmunoprecipitation (MI:0006)

MINT-7216175: SMRT (uniprotkb:Q9Y618) physically interacts (MI:0914) with Bag1 (uniprotkb:Q99933) by anti bait coimmunoprecipitation (MI:0006)

Abbreviations: Bag-1, Bcl-2 associated athanogene 1, GR, glucocorticoid receptor, GRmt, glucocorticoid receptor K496L/I497G mutant, Hsp, heat shock protein, hMTIIa, human metallothionein IIa, ChIP, chromatin immunoprecipitation, siRNA, small interfering RNA, IB, immunoblot, GRE, glucocorticoid response element, AR, androgen receptor, NcoR, nuclear receptor corepressor, SMRT, silencing mediator for retinoic acid and thyroid hormone receptor, HDAC, histone deacetylase