High impact information on Pparbp

• Thyroid hormone-induced juxtaposition of regulatory elements/factors and chromatin remodeling of Crabp1 dependent on MED1/TRAP220 [1].
• A MED1/TRAP220-containing Mediator complex constitutively occupies the GC box region but not the TRE, serving as a nexus for distal and proximal factors [1].
• All these events are abolished in Med1/Trap220 null cells, indicating a key role for TRAP/Mediator in these processes [1].
• Involvement of the TRAP220 component of the TRAP/SMCC coactivator complex in embryonic development and thyroid hormone action [2].
• Ablation of the murine Trap220 gene revealed that null mutants die during an early gestational stage with heart failure and exhibit impaired neuronal development with extensive apoptosis [2].

Biological context of Pparbp

• During early embryonic development, PPARgamma, SRC-1, and PBP are differentially expressed, with only limited cell types displaying overlapping expression [3].
• The expression of both SRC-1 and PBP is prominent in the breast epithelium of nonpregnant, pregnant, and lactating mice, whereas PPARgamma expression appeared prominent during lactation [3].
• Through expression profiling of knockout embryos, we observed altered expression of genes known to affect placental development, including the peroxisome proliferator-activated receptor-binding protein (Pparbp) [4].
• These data indicate that PRIP, like PBP, is a downstream regulator of PPARgamma-mediated adipogenesis and that both these coactivators are required for the successful completion of adipogenic program [5].
• Transcription coactivator PBP, the peroxisome proliferator-activated receptor (PPAR)-binding protein, is required for PPARalpha-regulated gene expression in liver [6].

Anatomical context of Pparbp

• PPARgamma and PBP are expressed in the transitional epithelium of urinary bladder and in brown adipose tissue, but not SRC-1 [3].
• In the colonic mucosa, PPARgamma expression occurs throughout the villi, whereas the expression of both SRC-1 and PBP is confined mostly to the crypts [3].
• Deletion of PBP/PPARBP, the gene for nuclear receptor coactivator peroxisome proliferator-activated receptor-binding protein, results in embryonic lethality [7].
• Disruption of the PBP/TRAP220 gene results in embryonic lethality around embryonic day 11.5 by affecting placental, cardiac, hepatic, and bone marrow development [6].
• In contrast, scattered PBP(+/+) hepatocytes in these livers showed DNA synthesis and were markedly hypertrophic with peroxisome proliferation in response to PPARalpha ligands [6].

Associations of Pparbp with chemical compounds

• Distinct roles of the steroid receptor coactivator 1 and of MED1 in retinoid-induced transcription and cellular differentiation [8].
• The TRAP220 component of the TRAP/SMCC complex, a mammalian homologof the yeast Mediator that shows diverse coactivation functions, interacts directly with nuclear receptors [2].
• Both the mammary ductal elongation in response to estrogen treatment and the mammary lobuloalveolar proliferation stimulated by estrogen plus progesterone were attenuated in PBP-deficient mammary glands [9].
• Glimepiride enhanced the recruitment of coactivator DRIP205 and dissociation of corepressors such as nuclear receptor corepressor and silencing mediator for retinoid and thyroid hormone receptors [10].
• Furthermore, flow cytometric analyses showed that HL-60 cells, human promyelocytic leukemia cell line, wherein TRAP220 was down-regulated, did not differentiate efficiently into monocytes and granulocytes by stimulation with 1,25-dihydroxyvitamin D(3) and all-trans retinoic acid, correspondingly [11].

Other interactions of Pparbp

• Differential expression of the peroxisome proliferator-activated receptor gamma (PPARgamma) and its coactivators steroid receptor coactivator-1 and PPAR-binding protein PBP in the brown fat, urinary bladder, colon, and breast of the mouse [3].
• PBP serves as an anchor for TRAP (thyroid hormone receptor-associated proteins)/mediator multisubunit cofactor transcription complex [6].
• PBP-deficient mammary epithelial cells expressed abundant beta-casein, whey acidic protein, and WDNM1 mRNA, indicating a relatively intact differentiated function [9].
• 5. The reduced expression in hypomorphs results in hepatic necrosis, defects in hematopoiesis, and hypoplasia of the ventricular myocardium, similar to that observed in TRAP220 null embryos at an earlier stage [12].
• We present evidence that the EDCs bisphenol A and phthalate activate ER-mediated transcription through interaction with TRAP220 [13].

Analytical, diagnostic and therapeutic context of Pparbp

• Using in situ hybridization we have examined expression of TRAP220 mRNA in the central nervous system during development and in adult rat and mouse brain [14].
• Furthermore, chromatin immunoprecipitation assays show that TRAP220/MED1-containing TRAP/Mediator complexes directly bind to the Aurora-A promoter in vivo [15].
• Using a crystallization solution containing sodium formate and PEG 3350 as precipitant, the heterodimer was cocrystallized with the promiscuous ligand 9-cis-retinoic acid (9C-RA) and a 13-residue fragment of the nuclear receptor interaction domain (NID) of the transcriptional coactivator TRAP220 [16].
• To determine the role of the MED-1 elements in the TS promoter, one or both elements were inactivated by site-directed mutagenesis and the effects on promoter function were determined [17].

References