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Current Opinion in Lipidology:
doi: 10.1097/MOL.0b013e328346230e
Lipid metabolism: Edited by Jeffrey S. Cohn

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

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

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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.

© 2011 Lippincott Williams & Wilkins, Inc.


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