Dephosphorylation of CCAAT/enhancer-binding protein beta by protein phosphatase 2A containing B56 delta is required at the early time of adipogenesis

Abstract

It is known that protein phosphatase 2A (PP2A) expression is increased in high-fat diet (HFD)-induced obese mice, but the role of PP2A in adipogenesis as well as obesity remains to be addressed. In this study, the role of PP2A in adipogenesis was explored. Preadipocytes were treated with okadaic acid (OA) during adipogenesis and the degree of adipogenesis was determined. The OA treatment blocked adipogenesis at the early time of adipogenesis, but not at the late time. In the early time of adipogenesis, CCAAT/enhancer-binding protein beta (C/EBP beta) activation is preceded by the expression of key adipogenic transcription factors including PPAR gamma and C/EBP alpha, which function at the late time of adipogenesis, and then C/EBP beta is degraded. However, the inhibition of PP2A by OA treatment sustained phosphorylation of C/EBP beta and delayed its degradation. In turn, PPAR gamma and C/EBP alpha activation was altered. Among the various regulatory B56 subunits consisting of PP2A holoenzyme, B56 delta was directly bound to C/EBP beta and was responsible for the dephosphorylation of C/EBP beta by PP2A. Taken together, these findings suggest that the phosphorylation of C/EBP beta after hormonal induction has to be inactivated by PP2A containing B56 delta at the early time of adipogenesis to allow the completion of adipogenesis. (C) 2014 Elsevier B.V. All rights reserved.