Modulation of Glucocorticoid-Receptor-Interacting Protein 1(GRIP1) Transcription and Coactivation Activities Through its own C-terminal Repression and Self-association

• Main Authors: Pei-Yao Liu, 呂姵瑤
• Other Authors: Shih-Ming Huang
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/39092542252018450622

碩士 === 國防醫學院 === 生物化學研究所 === 94 === GRIP1 (glucocorticoid-receptor-interacting protein 1), a p160 family nuclear receptor (NR) coactivator, possesses at least two autonomous activation domains (ADs) in the C-terminal region, AD1 and AD2. AD1 activity appears to be mediated by CBP/p300, whereas AD2 activity is apparently mediated through CARM1 (coactivator-associated arginine methyltransferase 1). The mechanisms responsible for the regulation of the activities of AD1 and AD2 are not well understood. This thesis provides several lines of evidence that indicate that the GRIP1 C-terminal region may be involved in regulation of its own transactivation and NR coactivation activities through primary self-association and a repression domain. I compared the effects of the GRIP1 C-terminus to other factors that can interact with GRIP1 C-terminus such as CARM1 and trichostatin A and proposed a regulatory mechanism that involves conformational changes to GRIP1 that are mediated through its intramolecular and intermolecular interactions and through repression domains in the presence of exogenous GRIP1 C-terminal fragments or other factors that interact with the C-terminus. In summary, our findings are the first to demonstrate that the structural components of GRIP1, especially those of the C-terminus, might functionally modulate its putative transactivation activities and NR coactivator functions.