• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

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

Mammalian Delta9 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 approximately 3 hours. Unexpectedly, proteasome inhibitors increased the half-life of SCD1 to approximately 6 hours. Endogenously expressed SCD1 in adipocyte-differentiated NIH 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.

Pubmed ID: 16723740

Authors

  • Kato H
  • Sakaki K
  • Mihara K

Journal

Journal of cell science

Publication Data

June 1, 2006

Associated Grants

None

Mesh Terms

  • Adenosine Triphosphatases
  • Animals
  • CHO Cells
  • Cell Line
  • Cells, Cultured
  • Cricetinae
  • Endoplasmic Reticulum
  • Gene Expression Regulation
  • HeLa Cells
  • Humans
  • Isoenzymes
  • Leupeptins
  • Mice
  • NIH 3T3 Cells
  • Nuclear Proteins
  • Proteasome Endopeptidase Complex
  • Stearoyl-CoA Desaturase
  • Ubiquitin