An adipogenic cofactor bound by the differentiation domain of PPARgamma.
Ligand activation of the nuclear receptor PPARgamma induces adipogenesis and increases insulin sensitivity, while activation of other PPAR isoforms (-alpha and -delta) induces little or no fat cell differentiation. Expression and activation of chimeras formed between PPARgamma and PPARdelta in fibroblasts has allowed us to localize a major domain of PPARgamma responsible for adipogenesis to the N-terminal 138 amino acids, a region with AF-1 transcriptional activity. Using this region of PPARgamma as bait, we have used a yeast two-hybrid screen to clone a novel protein, termed PGC-2, containing a partial SCAN domain. PGC-2 binds to and increases the transcriptional activity of PPARgamma but does not interact with other PPARs or most other nuclear receptors. Ectopic expression of PGC-2 in preadipocytes containing endogenous PPARgamma causes a dramatic increase in fat cell differentiation at both the morphological and molecular levels. These results suggest that interactions between PGC-2, a receptor isoform-selective cofactor and PPARgamma contribute to the adipogenic action of this receptor.
Dana-Farber Cancer Institute, 44 Binney Street Boston, MA 02115, USA.
G
G
Castillo
R P
RP
Brun
J K
JK
Rosenfield
S
S
Hauser
C W
CW
Park
A E
AE
Troy
M E
ME
Wright
B M
BM
Spiegelman
D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001391:Azo Compounds; D001483:Base Sequence; D002454:Cell Differentiation; D002460:Cell Line; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013379:Substrate Specificity; D015534:Trans-Activators; D014157:Transcription Factors / Q000819:agonists / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics; D014162:Transfection; D015003:Yeasts / Q000235:genetics
D001391:Azo Compounds; D020033:Protein Isoforms; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; C120815:Scand1 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C011049:oil red O