Lipin1 regulates PPAR{gamma} transcriptional activity

Peroxisome proliferator-activated receptor-γ (PPARγ) is a master transcription factor involved in adipogenesis through regulating adipocyte-specific gene expression. Recently, lipin1 is known to act as a key factor for the adipocyte maturation and maintenance with modulating C/EBPα and PPARγ network. However, the precise mechanism by which lipin1 affects transcriptional activity of PPARγ is largely unknown. The present study revealed that lipin1 activates PPARγ by releasing corepressors, nuclear receptor corepressor 1 (NcoR1) and silencing mediator of retinoid and thyroid hormone receptors (SMRT), from PPARγ in the absence of ligand, rosiglitazone. Also, we identified a novel lipin1 transcriptional activation domain (TAD), between residues 217 to 399, which is critical for the activation of PPARγ but not PPARα. Furthermore, this TAD is unique to lipin1 since this region does not show any homology with other lipin isoforms; lipin2 and lipin3. Activity of the lipin1 TAD is enhanced by p300 and SRC-1, but not by PCAF and PGC-1α. The physical interaction between lipin1 and PPARγ occurs at the lipin1 C-terminal region from residues 825 to 926, where the VXXLL motif at residue 885 is critical for binding with and the activation of PPARγ. The action of lipin1 as a coactivator of PPARγ enhanced the adipocyte differentiation, where TAD and VXXLL motif played the critical role but the catalytic a...
Source: BJ Gene - Category: Biochemistry Authors: Tags: BJ Metabolism Source Type: research