A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis.

@article{Goodwin2000ARC,
  title={A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis.},
  author={Bryan Goodwin and S A Jones and R. Reyn Price and Mike A Watson and D. D. Mckee and Linda B. Moore and Cristin M. Galardi and J. Gerald Wilson and Michelle Lewis and Matthew E. Roth and Patrick R. Maloney and Timothy M. Willson and Steven A. Kliewer},
  journal={Molecular cell},
  year={2000},
  volume={6 3},
  pages={
          517-26
        }
}
Bile acids repress the transcription of cytochrome P450 7A1 (CYP7A1), which catalyzes the rate-limiting step in bile acid biosynthesis. Although bile acids activate the farnesoid X receptor (FXR), the mechanism underlying bile acid-mediated repression of CYP7A1 remained unclear. We have used a potent, nonsteroidal FXR ligand to show that FXR induces expression of small heterodimer partner 1 (SHP-1), an atypical member of the nuclear receptor family that lacks a DNA-binding domain. SHP-1… Expand
Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors.
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Repression of the promoter activity mediated by liver receptor homolog-1 through interaction with ku proteins.
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Ku proteins interacted with not only LRH-1 but various nuclear receptors, such as the estrogen receptor, PPAR, and Rev-erb and suppressed the coactivating effect of peroxisome proliferator-activated receptor (PPAR) gamma coactivator-1alpha (PGC-1 alpha) on the LRh-1-mediated SHP promoter activity. Expand
PIASy inhibits LRH-1-dependent CYP11A1 expression by competing for SRC-1 binding.
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TLDR
An elaborate autoregulatory cascade mediated by nuclear receptors for the maintenance of hepatic cholesterol catabolism is revealed, showing that repression is coordinately regulated by a triumvirate of nuclear receptors, including the bile acid receptor, FXR, and the promoter-specific repressor, SHP. Expand
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