TRB3 links the E3 ubiquitin ligase COP1 to lipid metabolism.

Journal Article (Journal Article)

During fasting, increased concentrations of circulating catecholamines promote the mobilization of lipid stores from adipose tissue in part by phosphorylating and inactivating acetyl-coenzyme A carboxylase (ACC), the rate-limiting enzyme in fatty acid synthesis. Here, we describe a parallel pathway, in which the pseudokinase Tribbles 3 (TRB3), whose abundance is increased during fasting, stimulates lipolysis by triggering the degradation of ACC in adipose tissue. TRB3 promoted ACC ubiquitination through an association with the E3 ubiquitin ligase constitutive photomorphogenic protein 1 (COP1). Indeed, adipocytes deficient in TRB3 accumulated larger amounts of ACC protein than did wild-type cells. Because transgenic mice expressing TRB3 in adipose tissue are protected from diet-induced obesity due to enhanced fatty acid oxidation, these results demonstrate how phosphorylation and ubiquitination pathways converge on a key regulator of lipid metabolism to maintain energy homeostasis.

Full Text

Duke Authors

Cited Authors

  • Qi, L; Heredia, JE; Altarejos, JY; Screaton, R; Goebel, N; Niessen, S; Macleod, IX; Liew, CW; Kulkarni, RN; Bain, J; Newgard, C; Nelson, M; Evans, RM; Yates, J; Montminy, M

Published Date

  • June 23, 2006

Published In

Volume / Issue

  • 312 / 5781

Start / End Page

  • 1763 - 1766

PubMed ID

  • 16794074

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.1123374


  • eng

Conference Location

  • United States