CSIR Central

E3 Ubiquitin Ligase E6AP Negatively Regulates Adipogenesis by Downregulating Proadipogenic Factor C/EBPalpha

IR@CDRI: CSIR-Central Drug Research Institute, Lucknow


Field	Value

Creator	Pal, Pooja Lochab, Savita Kanaujiya, J K Kapoor, Isha Sanyal, Sabyasachi Behre, Gerhard Trivedi, A K

Date	2013-07-05T06:49:08Z 2013-07-05T06:49:08Z 2013

Identifier	PLoS ONE 8(6): e65330 http://hdl.handle.net/123456789/1079

Description	CCAAT/Enhancer Binding Protein Alpha (C/EBPa) is a key transcription factor involved in the adipocyte differentiation. Here for the first time we demonstrate that E6AP, an E3 ubiquitin ligase inhibits adipocyte differentiation in 3T3-L1 cells as revealed by reduced lipid staining with oil red. Knock down of E6AP in mouse 3T3L1 preadipocytes is sufficient to convert them to adipocytes independent of external hormonal induction. C/EBPa protein level is drastically increased in E6AP deficient 3T3L1 preadipocytes while inverse is observed when wild type E6AP is over expressed. We show that transient transfection of wild type E6AP downregulates C/EBPa protein expression in a dose dependent manner while catalytically inactive E6AP-C843A rather stabilizes it. In addition, wild type E6AP inhibits expression of proadipogenic genes while E6APC843A enhances them. More importantly, overexpression of E6AP-C843A in mesenchymal progenitor cells promotes accumulation of lipid droplets while there is drastically reduced lipid droplet formation when E6AP is over expressed. Taken together, our finding suggests that E6AP may negatively control adipogenesis by inhibiting C/EBPa expression by targeting it to ubiquitin-proteasome pathway for degradation.

Format	910227 bytes application/pdf

Language	en

Relation	C.D.R.I. Communication No. 8426

Subject	3T3-L1 C/EBPα E6AP Adipocyte Differentiation Ubiquitination

Title	E3 Ubiquitin Ligase E6AP Negatively Regulates Adipogenesis by Downregulating Proadipogenic Factor C/EBPalpha

Type	Article