Coactivator PRIP, the peroxisome proliferator-activated receptor-interacting protein, is a modulator of placental, cardiac, hepatic, and embryonic development.
Nuclear receptor coactivator PRIP (peroxisome proliferator-activated receptor (PPAR gamma)-interacting protein) and PRIP-interacting protein with methyltransferase activity, designated PIMT, appear to serve as linkers between cAMP response element-binding protein-binding protein (CBP)/p300-anchored and PBP (PPAR gamma-binding protein)-anchored coactivator complexes involved in the transcriptional activity of nuclear receptors. To assess the biological significance of PRIP, we disrupted the PRIP gene in mice by homologous recombination. Mice nullizygous for PRIP died between embryonic day 11.5 and 12.5 (postcoitum) due in most part to defects in the development of placenta, heart, liver, nervous system, and retardation of embryonic growth. Transient transfection assays using fibroblasts isolated from PRIP(-/-) embryos revealed a significant decrease in the capacity for ligand-dependent transcriptional activation of retinoid X receptor alpha and to a lesser effect on PPAR gamma transcriptional activity. These observations indicate that PRIP like PBP, CBP, and p300 is an essential and nonredundant coactivator.
Zhu
Yi-Jun
YJ
Department of Pathology, Northwestern University, the Feinberg School of Medicine, Chicago, Illinois 60611-3008, USA.
Crawford
Susan E
SE
Stellmach
Veronica
V
Dwivedi
Rama S
RS
Rao
M Sambasiva
MS
Gonzalez
Frank J
FJ
Qi
Chao
C
Reddy
Janardan K
JK
D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D017931:DNA Primers; D005314:Embryonic and Fetal Development / Q000502:physiology*; D005313:Fetal Death; D005317:Fetal Growth Retardation; D006321:Heart / Q000196:embryology*; D008099:Liver / Q000196:embryology*; D056913:Mediator Complex Subunit 1; D051379:Mice; D018345:Mice, Knockout; D010920:Placenta / Q000196:embryology*; D014157:Transcription Factors; D015533:Transcriptional Activation / Q000502:physiology
D002352:Carrier Proteins; D017931:DNA Primers; C538856:Med1 protein, mouse; D056913:Mediator Complex Subunit 1; D014157:Transcription Factors