Regulation of Bile Acid Biosynthesis by Orphan Nuclear Receptor Small Heterodimer Partner
Miao, Ji
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https://hdl.handle.net/2142/86322
Description
Title
Regulation of Bile Acid Biosynthesis by Orphan Nuclear Receptor Small Heterodimer Partner
Author(s)
Miao, Ji
Issue Date
2008
Doctoral Committee Chair(s)
Kemper, Jongsook K.
Department of Study
Cell and Developmental Biology
Discipline
Cell and Developmental Biology
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Cell
Language
eng
Abstract
These combined studies should greatly advance our understanding of how bile acid biosynthesis is regulated in both SHP-dependent and SHP-independent pathways. Importantly, these studies for the first time demonstrate that SHP has a short half-life of 20 to 30 minutes. Bile acids and FGF15/19 signaling pathways, and SHP ligand can dramatically increase SHP protein stability and abnormal regulation of SHP protein stability is associated with pathological disease conditions, indicating that regulation of SHP protein stability is a critical mechanism to regulate SHP activity. Since SHP plays a critical role in diverse cellular pathways, including bile acid/cholesterol and lipid/glucose homeostasis, and cell proliferation, this study to define how SHP activity is modulated by bile acids, FGF15/19 and its ligands, may reveal novel molecular targets for treating disorders in which SHP plays a key regulatory role. (Abstract shortened by UMI.).
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