title: Modulation of glucocorticoid receptor-interacting protein 1 (GRIP1) transactivation and co-activation activities through its C-terminal repression and self-association domains.
abstract: 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.
authors.affiliation: Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Pei-Yao
authors.initials: PY
authors.lastname: Liu
authors.forename: Tsai-Yuan
authors.initials: TY
authors.lastname: Hsieh
authors.forename: Wei-Yuan
authors.initials: WY
authors.lastname: Chou
authors.forename: Shih-Ming
authors.initials: SM
authors.lastname: Huang
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000502:physiology; D006801:Humans; D051958:Nuclear Receptor Coactivator 2 / Q000235:genetics* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; D051958:Nuclear Receptor Coactivator 2; D006655:Histone Deacetylases