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Coactivator PRIP, the Peroxisome Proliferator-activated Receptor-interacting Protein, Is a Modulator of Placental, Cardiac, Hepatic, and Embryonic Development

2003; Elsevier BV; Volume: 278; Issue: 3 Linguagem: Inglês

10.1074/jbc.c200634200

1083-351X

Yi-Jun Zhu, Susan E. Crawford, Veronica Stellmach, R.S. Dwivedi, Mahendra S. Rao, Frank J. Gonzalez, Chao Qi, Janardan K. Reddy,

Metabolism, Diabetes, and Cancer

Nuclear receptor coactivator PRIP (peroxisome proliferator-activated receptor (PPARγ)-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 (PPARγ-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 α and to a lesser effect on PPARγ transcriptional activity. These observations indicate that PRIP like PBP, CBP, and p300 is an essential and nonredundant coactivator.