PMID- 10334992
OWN - NLM
STAT- MEDLINE
DCOM- 19990618
LR  - 20190619
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 284
IP  - 5418
DP  - 1999 May 21
TI  - Identification of a nuclear receptor for bile acids.
PG  - 1362-5
AB  - Bile acids are essential for the solubilization and transport of dietary lipids
      and are the major products of cholesterol catabolism. Results presented here show
      that bile acids are physiological ligands for the farnesoid X receptor (FXR), an 
      orphan nuclear receptor. When bound to bile acids, FXR repressed transcription of
      the gene encoding cholesterol 7alpha-hydroxylase, which is the rate-limiting
      enzyme in bile acid synthesis, and activated the gene encoding intestinal bile
      acid-binding protein, which is a candidate bile acid transporter. These results
      demonstrate a mechanism by which bile acids transcriptionally regulate their
      biosynthesis and enterohepatic transport.
FAU - Makishima, M
AU  - Makishima M
AD  - Howard Hughes Medical Institute and Department of Pharmacology, University of
      Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX
      75235-9050, USA.
FAU - Okamoto, A Y
AU  - Okamoto AY
FAU - Repa, J J
AU  - Repa JJ
FAU - Tu, H
AU  - Tu H
FAU - Learned, R M
AU  - Learned RM
FAU - Luk, A
AU  - Luk A
FAU - Hull, M V
AU  - Hull MV
FAU - Lustig, K D
AU  - Lustig KD
FAU - Mangelsdorf, D J
AU  - Mangelsdorf DJ
FAU - Shan, B
AU  - Shan B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Bile Acids and Salts)
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Ligands)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Organic Anion Transporters, Sodium-Dependent)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Symporters)
RN  - 0 (Transcription Factors)
RN  - 0 (bile acid binding proteins)
RN  - 0C5V0MRU6P (farnesoid X-activated receptor)
RN  - 0GEI24LG0J (Chenodeoxycholic Acid)
RN  - 145420-23-1 (sodium-bile acid cotransporter)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 1.1.- (Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.357 (AKR1C2 protein, human)
RN  - EC 1.14.14.23 (Cholesterol 7-alpha-Hydroxylase)
RN  - EC 2.3.1.48 (Histone Acetyltransferases)
RN  - EC 2.3.1.48 (NCOA1 protein, human)
RN  - EC 2.3.1.48 (Ncoa1 protein, mouse)
RN  - EC 2.3.1.48 (Nuclear Receptor Coactivator 1)
SB  - IM
CIN - Science. 1999 May 21;284(5418):1285-6. PMID: 10383308
MH  - Animals
MH  - Bile Acids and Salts/biosynthesis/*metabolism
MH  - Biological Transport
MH  - Carrier Proteins/*genetics/metabolism
MH  - Cell Line
MH  - Chenodeoxycholic Acid/*metabolism
MH  - Cholesterol/metabolism
MH  - Cholesterol 7-alpha-Hydroxylase/*genetics
MH  - DNA-Binding Proteins/chemistry/genetics/*metabolism
MH  - Gene Expression Regulation
MH  - Histone Acetyltransferases
MH  - Homeostasis
MH  - Humans
MH  - *Hydroxysteroid Dehydrogenases
MH  - Ligands
MH  - Liver/metabolism
MH  - *Membrane Glycoproteins
MH  - Mice
MH  - Nuclear Receptor Coactivator 1
MH  - *Organic Anion Transporters, Sodium-Dependent
MH  - Receptors, Cytoplasmic and Nuclear/chemistry/genetics/*metabolism
MH  - *Symporters
MH  - Transcription Factors/chemistry/genetics/*metabolism
MH  - Transfection
MH  - Tumor Cells, Cultured
EDAT- 1999/05/21 00:00
MHDA- 1999/05/21 00:01
CRDT- 1999/05/21 00:00
PHST- 1999/05/21 00:00 [pubmed]
PHST- 1999/05/21 00:01 [medline]
PHST- 1999/05/21 00:00 [entrez]
AID - 10.1126/science.284.5418.1362 [doi]
PST - ppublish
SO  - Science. 1999 May 21;284(5418):1362-5. doi: 10.1126/science.284.5418.1362.