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  Identification of farnesoid X receptor beta as a novel mammalian nuclear receptor sensing lanosterol

Otte, K., Kranz, H., Kober, I., Thompson, P., Hoefer, M., Haubold, B., et al. (2003). Identification of farnesoid X receptor beta as a novel mammalian nuclear receptor sensing lanosterol. Molecular and Cellular Biology, 23(3), 864-872. doi:10.1128/MCB.23.3.864-872.2003.

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Otte, K.1, Author
Kranz, H.1, Author
Kober, I.1, Author
Thompson, P.1, Author
Hoefer, M.1, Author
Haubold, B.2, Author           
Remmel, B.1, Author
Voss, H.1, Author
Kaiser, C.1, Author
Albers, M.1, Author
Cheruvallath, Z.1, Author
Jackson, D.1, Author
Casari, G.1, Author
Koegl, M.1, Author
Paabo, S.1, Author
Mous, J.1, Author
Kremoser, C.1, Author
Deuschle, U.1, Author
Affiliations:
1external, ou_persistent22              
2External, ou_persistent22              

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 Abstract: Nuclear receptors are ligand-modulated transcription factors. On the basis of the completed human genome sequence, this family was thought to contain 48 functional members. However, by mining human and mouse genomic sequences, we identified FXRbeta as a novel family member. It is a functional receptor in mice, rats, rabbits, and dogs but constitutes a pseudogene in humans and primates. Murine FXRbeta is widely coexpressed with FXR in embryonic and adult tissues. It heterodimerizes with RXRalpha and stimulates transcription through specific DNA response elements upon addition of 9-cis-retinoic acid. Finally, we identified lanosterol as a candidate endogenous ligand that induces coactivator recruitment and transcriptional activation by mFXRbeta. Lanosterol is an intermediate of cholesterol biosynthesis, which suggests a direct role in the control of cholesterol biosynthesis in nonprimates. The identification of FXRbeta as a novel functional receptor in nonprimate animals sheds new light on the species differences in cholesterol metabolism and has strong implications for the interpretation of genetic and pharmacological studies of FXR-directed physiologies and drug discovery programs.

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 Dates: 2003-022003-02
 Publication Status: Issued
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Title: Molecular and Cellular Biology
  Other : Mol Cell Biol
Source Genre: Journal
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Publ. Info: Washington, DC : American Society for Microbiology (ASM)
Pages: - Volume / Issue: 23 (3) Sequence Number: - Start / End Page: 864 - 872 Identifier: ISSN: 0270-7306 (print)
ISSN: 1098-5549 (online)
CoNE: https://pure.mpg.de/cone/journals/resource/954925502188