Regulation of diacylglycerol acyltransferase 2 protein stability by gp78‐associated endoplasmic‐reticulum‐associated degradation. (6th June 2014)

• Record Type: Journal Article
• Authors: Choi, Kwangman; Kim, Hyeongki; Kang, Hyunju; Lee, So‐Young; Lee, Sang Jun; Back, Sung Hoon; Lee, Seo Hyun; Kim, M. Sun; Lee, Jeong Eun; Park, Ju Young; Kim, Jiye; Kim, Sunhong; Song, Jae‐Hyung; Choi, Yura; Lee, Suui; Lee, Hyun‐Jun; Kim, Jong Heon; Cho, Sungchan
• Is Part Of: FEBS journal. Volume 281:Number 13(2014)
• Page Start: 3048
• Page End: 3060
• Publication Date: 2014-06-06
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.12841
• Languages: English
• ISSNs: 1742-464X

Abstract

<abstract abstract-type="main" id="febs12841-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="febs12841-sec-0001" sec-type="section"> <p>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.</p> </sec> <sec id="febs12841-sec-0002" sec-type="section"> <title>Structured digital abstract</title> <p> <list id="febs12841-list-0001" list-type="bullet"> <list-item> <p> <ext-link ext-link-type="uri" xlink:href="http://www.uniprot.org/uniprot/Q96PD7" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">DGAT2</ext-link> <ext-link ext-link-type="uri" xlink:href="http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0915" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">physically interacts</ext-link> with <ext-link ext-link-type="uri" xlink:href="http://www.uniprot.org/uniprot/Q9UKV5" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">gp78</ext-link> by <ext-link ext-link-type="uri" xlink:href="http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0007" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">anti tag coimmunoprecipitation</ext-link> (<ext-link ext-link-type="uri" xlink:href="http://www.ebi.ac.uk/intact/interaction/EBI-9520083" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">View interaction</ext-link>)</p> </list-item> <list-item> <p> <ext-link ext-link-type="uri" xlink:href="http://www.uniprot.org/uniprot/Q96PD7" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">DGAT2</ext-link> <ext-link ext-link-type="uri" xlink:href="http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0915" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">physically interacts</ext-link> with <ext-link ext-link-type="uri" xlink:href="http://www.uniprot.org/uniprot/P55072" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">VCP</ext-link> by <ext-link ext-link-type="uri" xlink:href="http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0007" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">anti tag coimmunoprecipitation</ext-link> (<ext-link ext-link-type="uri" xlink:href="http://www.ebi.ac.uk/intact/interaction/EBI-9519939" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">View interaction</ext-link>)</p> </list-item> </list> </p> </sec> </abstract>