The Lim Protein Ajuba Promotes Adipogenesis By Enhancing Ppar Gamma And P300/Cbp Interaction

Adipocytes play a vital role in energy homeostasis and adipogenesis is a hierarchically regulated cellular differentiation process, in which the precursor mesenchymal stem cells are differentiated into mature adipocytes. Here, we report Ajuba is an important regulator of adipocyte differentiation by functioning as an obligate co-activator of PPAR gamma. Ajuba binds the DNA-binding domain of PPAR gamma via its preLIM region in a ligand-independent manner. Depletion of Ajuba in 3T3-L1 cells decreases PPAR gamma target gene expression and results in delayed adipogenic differentiation. Conversely, stable overexpression of Ajuba in 3T3-L1 cells increases PPAR gamma target gene expression and accelerates adipogenic differentiation. Mechanistic investigations demonstrate that Ajuba recruits p300/CBP via its LIM domain and facilitates p300/CBP binding to PPAR gamma. Moreover, Ajuba, PPAR gamma, p300/CBP can cooperatively occupy the PPAR gamma target promoters and concomitantly increases histone acetylation at these loci. Collectively, these data suggest that Ajuba is a co-activator constitutively associated with PPAR gamma and may be a potential therapeutic target for PPAR gamma-mediated metabolic disorders.