دورية أكاديمية
أعرض في EDS

An ERAD-independent role for rhomboid pseudoprotease Dfm1 in mediating sphingolipid homeostasis.

التفاصيل البيبلوغرافية
العنوان: An ERAD-independent role for rhomboid pseudoprotease Dfm1 in mediating sphingolipid homeostasis.
المؤلفون: Bhaduri S; Department of Cell and Developmental Biology, School of Biological Sciences, University of California San Diego, La Jolla, CA, USA., Aguayo A; Department of Cell and Developmental Biology, School of Biological Sciences, University of California San Diego, La Jolla, CA, USA., Ohno Y; Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan., Proietto M; Department of Cell and Developmental Biology, School of Biological Sciences, University of California San Diego, La Jolla, CA, USA., Jung J; Department of Cell and Developmental Biology, School of Biological Sciences, University of California San Diego, La Jolla, CA, USA., Wang I; Department of Cell and Developmental Biology, School of Biological Sciences, University of California San Diego, La Jolla, CA, USA., Kandel R; Department of Cell and Developmental Biology, School of Biological Sciences, University of California San Diego, La Jolla, CA, USA., Singh N; Department of Cell and Developmental Biology, School of Biological Sciences, University of California San Diego, La Jolla, CA, USA., Ibrahim I; Department of Cell and Developmental Biology, School of Biological Sciences, University of California San Diego, La Jolla, CA, USA., Fulzele A, Bennett EJ; Department of Cell and Developmental Biology, School of Biological Sciences, University of California San Diego, La Jolla, CA, USA., Kihara A; Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan., Neal SE; Department of Cell and Developmental Biology, School of Biological Sciences, University of California San Diego, La Jolla, CA, USA.
المصدر: The EMBO journal [EMBO J] 2023 Feb 15; Vol. 42 (4), pp. e112275. Date of Electronic Publication: 2022 Nov 09.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8208664 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1460-2075 (Electronic) Linking ISSN: 02614189 NLM ISO Abbreviation: EMBO J Subsets: MEDLINE
أسماء مطبوعة: Publication: 2024- : [London] : Nature Publishing Group
Original Publication: Eynsham, Oxford, England : Published for the European Molecular Biology Organization by IRL Press, [c1982-
مواضيع طبية MeSH: Endoplasmic Reticulum-Associated Degradation* , Sphingolipids*/metabolism, Humans ; Ubiquitin/metabolism ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Homeostasis
مستخلص: Nearly one-third of nascent proteins are initially targeted to the endoplasmic reticulum (ER), where they are correctly folded and assembled before being delivered to their final cellular destinations. To prevent the accumulation of misfolded membrane proteins, ER-associated degradation (ERAD) removes these client proteins from the ER membrane to the cytosol in a process known as retrotranslocation. Our previous work demonstrated that rhomboid pseudoprotease Dfm1 is involved in the retrotranslocation of ubiquitinated membrane integral ERAD substrates. Herein, we found that Dfm1 associates with the SPOTS complex, which is composed of serine palmitoyltransferase (SPT) enzymes and accessory components that are critical for catalyzing the first rate-limiting step of the sphingolipid biosynthesis pathway. Furthermore, Dfm1 employs an ERAD-independent role for facilitating the ER export and endosome- and Golgi-associated degradation (EGAD) of Orm2, which is a major antagonist of SPT activity. Given that the accumulation of human Orm2 homologs, ORMDLs, is associated with various pathologies, our study serves as a molecular foothold for understanding how dysregulation of sphingolipid metabolism leads to various diseases.
(© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)
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معلومات مُعتمدة: T32 GM133351 United States GM NIGMS NIH HHS; GT15096 United States HHMI Howard Hughes Medical Institute; R25 HL145817 United States HL NHLBI NIH HHS; DP2GM119132 United States GM NIGMS NIH HHS; T32 HL007444 United States HL NHLBI NIH HHS; 1R35GM133565-01 United States GM NIGMS NIH HHS; 5R01GM136994-02 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: ERAD; Orm1/2; endoplasmic reticulum; rhomboid pseudoprotease; sphingolipid homeostasis
المشرفين على المادة: 0 (Sphingolipids)
0 (Ubiquitin)
0 (Membrane Proteins)
تواريخ الأحداث: Date Created: 20221109 Date Completed: 20230216 Latest Revision: 20240608
رمز التحديث: 20240608
مُعرف محوري في PubMed: PMC9929635
DOI: 10.15252/embj.2022112275
PMID: 36350249
قاعدة البيانات: MEDLINE
الوصف
تدمد:1460-2075
DOI:10.15252/embj.2022112275