In:
The FEBS Journal, Wiley, Vol. 281, No. 13 ( 2014-07), p. 3048-3060
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 ). DGAT 2, one of the two DGAT enzymes, is barely detectable in cells, even though its m RNA transcripts are maintained at considerable levels. However, little is known about how DGAT 2 expression is altered by protein stability. DGAT 2 was highly unstable in cells and was rapidly degraded by proteasomes in an ubiquitin‐dependent manner. Deletion mutation analysis identified transmembrane domain 1 ( TMD 1) as a protein degradation signal. TMD 1 is also important for ER localization of DGAT 2. Moreover, DGAT 2 interacted with p97/ VCP , a crucial component of the ER ‐associated degradation ( ERAD ) pathway, and polyubiquitinated DGAT 2 accumulated following treatment with an ERAD inhibitor. Furthermore, gp78, an E3 ligase involved in ERAD , regulates the degradation of DGAT 2 through direct interactions and ubiquitination. Consequently, the stabilization of DGAT 2 increased the number of lipid droplets in hepatic cells. Therefore, DGAT 2 is regulated by gp78‐associated ERAD at the post‐translational level. Structured digital abstract DGAT2 physically interacts with gp78 by anti tag coimmunoprecipitation ( View interaction ) DGAT2 physically interacts with VCP by anti tag coimmunoprecipitation ( View interaction )
Type of Medium:
Online Resource
ISSN:
1742-464X
,
1742-4658
DOI:
10.1111/febs.2014.281.issue-13
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
2172518-4
SSG:
12
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