title: Small heterodimer partner, an orphan nuclear receptor, augments peroxisome proliferator-activated receptor gamma transactivation.
abstract: Small heterodimer partner (SHP, NR0B2) is an atypical orphan nuclear receptor that inhibits transcriptional activation by several other nuclear receptors. We recently reported that mutations in the SHP gene are associated with insulin resistance. In the present study, we demonstrated that the SHP gene is expressed in adipose tissues. A reporter gene assay showed that a gene product of SHP increased the transcriptional activation of peroxisome proliferator-activated receptor (PPAR) gamma. SHP-mediated activation of PPARgamma was observed both in the presence and absence of the ligand of PPARgamma. Immunoprecipitation and glutathione S-transferase pull-down assay showed that SHP directly bound to PPARgamma and competed with nuclear receptor corepressor for binding to PPARgamma. Serial deletion studies indicated that the C terminus of SHP is important for PPARgamma activation. Mutant SHP proteins, which are found in naturally occurring mutation, showed less enhancing activity for PPARgamma than wild-type SHP. Our results suggest that SHP may act as an endogenous enhancer of PPARgamma.
authors.affiliation: Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nishizawa
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamagata
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kuriyama
authors.forename: Ken
authors.initials: K
authors.lastname: Kishida
authors.forename: Kikuko
authors.initials: K
authors.lastname: Hotta
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nagaretani
authors.forename: Norikazu
authors.initials: N
authors.lastname: Maeda
authors.forename: Morihiro
authors.initials: M
authors.lastname: Matsuda
authors.forename: Shinji
authors.initials: S
authors.lastname: Kihara
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Nishigori
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tomura
authors.forename: David D
authors.initials: DD
authors.lastname: Moore
authors.forename: Jun
authors.initials: J
authors.lastname: Takeda
authors.forename: Tohru
authors.initials: T
authors.lastname: Funahashi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsuzawa
mesh_terms: D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D017930:Genes, Reporter; D051557:Hepatocyte Nuclear Factor 4; D006801:Humans; D008297:Male; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D051557:Hepatocyte Nuclear Factor 4; C403128:MLX protein, human; D010750:Phosphoproteins; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; C501970:Tcfl4 protein, mouse; D014157:Transcription Factors; C099713:nuclear receptor subfamily 0, group B, member 2