Unsaturated fatty acids inhibit proteasomal degradation of insig-1 at a postubiquitination step

No Lee Joon, Xiangyu Zhang, Jamison D. Feramisco, Yi Gong, Jin Ye

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Proteasomes mediate the regulated degradation of Insig-1, a membrane protein of the endoplasmic reticulum (ER) that plays a crucial role in lipid metabolism. We showed previously that sterols inhibit this degradation by blocking ubiquitination of Insig-1. Here we show that unsaturated fatty acids stabilize Insig-1 without affecting its ubiquitination. Instead unsaturated fatty acids inhibit extraction of ubiquitinated Insig-1 from membranes, a process known to be mediated by valosin-containing protein and necessary for ER-associated degradation. Valosin-containing protein is recruited to Insig-1 through the action of another protein, Ubxd8. Unsaturated fatty acids block the binding between Ubxd8 and Insig-1, thereby abrogating the membrane extraction of Insig-1. Unsaturated fatty acid-mediated stabilization of Insig-1 enhances the ability of sterols to inhibit proteolytic activation of SREBP-1, which activates transcription of genes involved in fatty acid synthesis. The current study provides a molecular mechanism for regulation of proteasome-mediated ER protein degradation at a postubiquitination step.

Original languageEnglish (US)
Pages (from-to)33772-33783
Number of pages12
JournalJournal of Biological Chemistry
Volume283
Issue number48
DOIs
StatePublished - Nov 28 2008

Fingerprint

Unsaturated Fatty Acids
Degradation
Ubiquitination
Sterols
Proteasome Endopeptidase Complex
Endoplasmic Reticulum
Endoplasmic Reticulum-Associated Degradation
Membranes
Transcription
Lipid Metabolism
Proteolysis
Membrane Proteins
Proteins
Fatty Acids
Stabilization
Genes
Chemical activation
CDC48 protein

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Unsaturated fatty acids inhibit proteasomal degradation of insig-1 at a postubiquitination step. / Joon, No Lee; Zhang, Xiangyu; Feramisco, Jamison D.; Gong, Yi; Ye, Jin.

In: Journal of Biological Chemistry, Vol. 283, No. 48, 28.11.2008, p. 33772-33783.

Research output: Contribution to journalArticle

Joon, No Lee ; Zhang, Xiangyu ; Feramisco, Jamison D. ; Gong, Yi ; Ye, Jin. / Unsaturated fatty acids inhibit proteasomal degradation of insig-1 at a postubiquitination step. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 48. pp. 33772-33783.
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