Ubiquitin-proteasome-dependent degradation of mammalian ER stearoyl-CoA desaturase

Hiroki Kato, Kenjiro Sakaki, Katsuyoshi Mihara

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Mammalian Δ9 stearoyl-CoA desaturase 1 (SCD1) is a key enzyme in the biosynthesis of mono-unsaturated fatty acids in the endoplasmic reticulum (ER). It is a short-lived multispanning ER membrane protein, reported to be degraded by the ubiquitin-proteasome-independent pathway. We have examined SCD1 protein degradation using cultured mammalian cells. Exogenously expressed SCD1 in CHO-K1 cells was localized to the ER and turned over with a half-life of ∼3 hours. Unexpectedly, proteasome inhibitors increased the half-life of SCD1 to ∼6 hours. Endogenously expressed SCD1 in adipocyte-differentiated NHI 3T3-L1 cells was also rapidly degraded in a proteasome inhibitor-sensitive manner. In the presence of proteasome inhibitors, polyubiquitylated SCD1 accumulated in the ER and interacted with AAA-ATPase p97, which is involved in ER-associated degradation (ERAD). The 66-residue N-terminal segment carrying the PEST sequence is mainly responsible for SCD1 degradation and this segment induced instability in an otherwise stable ER membrane protein. Furthermore, SCD1 was degraded constitutively irrespective of the cellular levels of unsaturated fatty acids, which strictly regulate SCD1 gene expression. These findings indicate that the ubiquitin-proteasome-dependent ERAD system is also involved in constitutive SCD1 degradation.

Original languageEnglish
Pages (from-to)2342-2353
Number of pages12
JournalJournal of Cell Science
Volume119
Issue number11
DOIs
Publication statusPublished - Jun 1 2006

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Stearoyl-CoA Desaturase
Proteasome Endopeptidase Complex
Ubiquitin
Endoplasmic Reticulum
Proteasome Inhibitors
Unsaturated Fatty Acids
Half-Life
Membrane Proteins
Endoplasmic Reticulum-Associated Degradation
3T3-L1 Cells
CHO Cells
Adipocytes
Proteolysis
Cultured Cells

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Ubiquitin-proteasome-dependent degradation of mammalian ER stearoyl-CoA desaturase. / Kato, Hiroki; Sakaki, Kenjiro; Mihara, Katsuyoshi.

In: Journal of Cell Science, Vol. 119, No. 11, 01.06.2006, p. 2342-2353.

Research output: Contribution to journalArticle

Kato, Hiroki ; Sakaki, Kenjiro ; Mihara, Katsuyoshi. / Ubiquitin-proteasome-dependent degradation of mammalian ER stearoyl-CoA desaturase. In: Journal of Cell Science. 2006 ; Vol. 119, No. 11. pp. 2342-2353.
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