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Science 23 June 2006:
Vol. 312. no. 5781, p. 1712
DOI: 10.1126/science.312.5781.1712f
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The protein known as TRB3 is a pseudokinase (a kinase-like protein that lacks kinase activity) synthesized in fasting animals. TRB3 modulates insulin signaling and is related to a Drosophila protein that coordinates mitosis and morphogenesis during development. Qi et al. (p. 1763; see the Perspective by Neels and Olefsky) find that overexpression of TRB3 in mice confers resistance to diet-induced obesity. This effect appears to be the result of decreased activity of acetyl-coenzyme A carboxylase (ACC) and consequent decreased synthesis of fatty acids. TRB3 directly interacts with ACC to promote its degradation via the E3 ubiquitin ligase constitutive photomorphogenic protein 1. Understanding the regulation of lipid metabolism may promote therapeutic strategies for the control of obesity.




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Science. ISSN 0036-8075 (print), 1095-9203 (online)