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Recent insights into the structure and function of comparative gene identification-58

Oberer, Monika; Boeszoermenyi, Andras; Nagy, Harald M; Zechner, Rudolf

Current Opinion in Lipidology: June 2011 - Volume 22 - Issue 3 - p 149–158
doi: 10.1097/MOL.0b013e328346230e
Lipid metabolism: Edited by Jeffrey S. Cohn

Purpose of review Comparative gene identification-58 (CGI-58) is an important player in lipid metabolism. It acts as activator of triglyceride hydrolases and as acyl-CoA-dependent lysophosphatidic acid acyltransferase. This review aims at establishing a structure–function relationship of this still rather enigmatic protein based on recent studies characterizing different functions of CGI-58.

Recent findings Novel studies confirm the important regulatory role of CGI-58 as activator of the triglyceride hydrolase adipose triglyceride lipase. New evidence, corroborated by the characterization of a CGI-58 knockout mouse model, also suggests the existence of yet unknown lipases that are activated by CGI-58. Additionally, CGI-58 was identified to exert acyl-CoA-dependent lysophosphatidic acid acyltransferase activity, which implies possible roles in triglyceride or phospholipid synthesis or signaling processes. Unlike mammalian CGI-58 proteins, orthologs from plants and yeast additionally act as weak triglyceride and phospholipid hydrolases. A first three-dimensional model was calculated and allows preliminary structural considerations for the functions of CGI-58.

Summary Despite important progress concerning the different biochemical functions of CGI-58, the physiological importance of these activities requires better characterization. Furthermore, three-dimensional structural data for CGI-58 are required to unveil the molecular mechanism of how CGI-58 acts as activator of lipases and exerts its enzymatic functions.

Institute of Molecular Biosciences, University of Graz, Graz, Austria

Correspondence to Monika Oberer, Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50, 8010 Graz, Austria Tel: +43 316 380 5483; e-mail: m.oberer@uni-graz.at

© 2011 Lippincott Williams & Wilkins, Inc.