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Regulation of diacylglycerol acyltransferase 2 protein stability by gp78-associated endoplasmic-reticulum-associated degradation
- Source :
- FEBS Journal. 281:3048-3060
- Publication Year :
- 2014
- Publisher :
- Wiley, 2014.
-
Abstract
- Triacylglycerol (TG) is the major form of stored energy in eukaryotic organisms and is synthesized by diacylglycerol acyltransferase (DGAT) in the endoplasmic reticulum (ER). DGAT2, one of the two DGAT enzymes, is barely detectable in cells, even though its mRNA transcripts are maintained at considerable levels. However, little is known about how DGAT2 expression is altered by protein stability. DGAT2 was highly unstable in cells and was rapidly degraded by proteasomes in an ubiquitin-dependent manner. Deletion mutation analysis identified transmembrane domain 1 (TMD1) as a protein degradation signal. TMD1 is also important for ER localization of DGAT2. Moreover, DGAT2 interacted with p97/VCP, a crucial component of the ER-associated degradation (ERAD) pathway, and polyubiquitinated DGAT2 accumulated following treatment with an ERAD inhibitor. Furthermore, gp78, an E3 ligase involved in ERAD, regulates the degradation of DGAT2 through direct interactions and ubiquitination. Consequently, the stabilization of DGAT2 increased the number of lipid droplets in hepatic cells. Therefore, DGAT2 is regulated by gp78-associated ERAD at the post-translational level.
- Subjects :
- Proteasome Endopeptidase Complex
macromolecular substances
Endoplasmic-reticulum-associated protein degradation
Biochemistry
Ubiquitin
Cell Line, Tumor
Lipid droplet
Enzyme Stability
Humans
Diacylglycerol O-Acyltransferase
Molecular Biology
Messenger RNA
biology
Endoplasmic reticulum
Ubiquitination
Endoplasmic Reticulum-Associated Degradation
Cell Biology
Lipid Metabolism
Protein Structure, Tertiary
Ubiquitin ligase
Receptors, Autocrine Motility Factor
Transmembrane domain
HEK293 Cells
Proteasome
Proteolysis
Hepatocytes
biology.protein
Subjects
Details
- ISSN :
- 1742464X
- Volume :
- 281
- Database :
- OpenAIRE
- Journal :
- FEBS Journal
- Accession number :
- edsair.doi.dedup.....09be45cf82f74a05ab49815fa9c026b3