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Modulation of glucocorticoid receptor‐interacting protein 1 (GRIP1) transactivation and co‐activation activities through its C‐terminal repression and self‐association domains
Author(s) -
Liu PeiYao,
Hsieh TsaiYuan,
Chou WeiYuan,
Huang ShihMing
Publication year - 2006
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2006.05231.x
Subject(s) - transactivation , psychological repression , activator (genetics) , glucocorticoid receptor , repressor , microbiology and biotechnology , coactivator , nuclear receptor , receptor , nuclear receptor coactivator 3 , nuclear receptor coactivator 1 , nuclear receptor coactivator 2 , chemistry , biology , transcription factor , biochemistry , gene , gene expression
Glucocorticoid receptor‐interacting protein 1 (GRIP1), a p160 family nuclear receptor co‐activator, possesses at least two autonomous activation domains (AD1 and AD2) in the C‐terminal region. AD1 activity appears to be mediated by CBP/p300, whereas AD2 activity is apparently mediated through co‐activator‐associated arginine methyltransferase 1 (CARM1). The mechanisms responsible for regulating the activities of AD1 and AD2 are not well understood. We provide evidence that the GRIP1 C‐terminal region may be involved in regulating its own transactivation and nuclear receptor co‐activation activities through primary self‐association and a repression domain. We also compared the effects of the GRIP1 C terminus with those of other factors that functionally interact with the GRIP1 C terminus, such as CARM1. Based on our results, we propose a regulatory mechanism involving conformational changes to GRIP1 mediated through its intramolecular and intermolecular interactions, and through modulation of the effects of co‐repressors on its repression domains. These are the first results to indicate that the structural components of GRIP1, especially those of the C terminus, might functionally modulate its putative transactivation activities and nuclear receptor co‐activator functions.