Chemistry Faculty Scholarship

Document Type

Article

Publication Date

8-22-2005

Publication Title

Journal of Biological Chemistry

Keywords

Post-translational regulation, Adipose differentiation-related protein

Abstract

Adipose differentiation-related protein (ADRP) is localized to lipid droplets in most mammalian cells. ADRP, proposed to regulate
fatty acid mobilization and lipid droplet formation, is linked to lipid accumulation in foam cells of human atherosclerotic
lesions. In this report, we show that ADRP protein accumulates in Chinese hamster ovary fibroblastic cells cultured in the
presence of oleic acid but is destabilized when fatty acid sources are removed from culture serum. The latter effect was blocked
by the proteasome inhibitor MG132, whereas inhibitors of other proteolytic processes were ineffective. Pulse-chase experiments
confirmed that ADRP degradation is inhibited by MG132. Conditions that stimulate ADRP degradation also promoted the covalent
modification of ADRP by ubiquitin, whereas the addition of oleic acid to culture media, which promotes triacylglycerol deposition,
blunted the appearance of ubiquitinated-ADRP. Treatment with MG132 increased the levels of ADRP associated with lipid droplets,
as well as throughout the cytosol. Finally, we demonstrate that the disappearance of ADRP protein after the onset of perilipin
expression during adipocyte differentiation is due to degradation by proteasomes Thus, proteolytic degradation of ADRP mediated
through the ubiquitin/proteasome pathway appears to be a major mode for the post-translational regulation of ADRP.

First Page

42841

Last Page

42847

Volume

280

Issue

52

DOI

10.1074/jbc.M506569200

Version

Publisher's Version

Peer Reviewed

1

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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