Universität zu Köln

Bock, Josephine ORCID: 0000-0001-6665-8137, Kuhnle, Nathalie, Knopf, Julia D., Landscheidt, Nina, Lee, Jin-Gu ORCID: 0000-0001-9477-6990, Ye, Yihong and Lemberg, Marius K. (2022). Rhomboid protease RHBDL4 promotes retrotranslocation of aggregation-prone proteins for degradation. Cell Reports, 40 (6). CAMBRIDGE: CELL PRESS. ISSN 2211-1247

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Abstract

Protein degradation is fundamentally important to ensure cell homeostasis. In the endoplasmic reticulum (ER), the ER-associated degradation (ERAD) pathway targets incorrectly folded and unassembled proteins for turnover by the cytoplasmic proteasome. Previously, we showed that the rhomboid protease RHBDL4, together with p97, mediates membrane protein degradation. However, whether RHBDL4 acts in concert with additional ERAD components is unclear, and its full substrate spectrum remains to be defined. Here, we show that, in addition to membrane proteins, RHBDL4 cleaves aggregation-prone luminal ERAD substrates. Since mutations of the RHBDL4 rhomboid domain led to stabilization of substrates at the cytoplasmic side, we hypothesize that, analogous to the homolog ERAD factor derlin, RHBDL4 is directly involved in substrate retrotranslocation. RHBDL4's interaction with the erlin ERAD complex and reciprocal interaction of rhomboid substrates with erlins suggest that RHBDL4 and erlins form a complex that clips substrates and thereby rescues aggregation-prone peptides in the ER from aggregation.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bock, Josephine UNSPECIFIED orcid.org/0000-0001-6665-8137 UNSPECIFIED Kuhnle, Nathalie UNSPECIFIED UNSPECIFIED UNSPECIFIED Knopf, Julia D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Landscheidt, Nina UNSPECIFIED UNSPECIFIED UNSPECIFIED Lee, Jin-Gu UNSPECIFIED orcid.org/0000-0001-9477-6990 UNSPECIFIED Ye, Yihong UNSPECIFIED UNSPECIFIED UNSPECIFIED Lemberg, Marius K. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-678335
DOI:	10.1016/j.celrep.2022.111175
Journal or Publication Title:	Cell Reports
Volume:	40
Number:	6
Date:	2022
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	2211-1247
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ER-ASSOCIATED DEGRADATION; CLASS-I MOLECULES; ENDOPLASMIC-RETICULUM; UBIQUITIN-LIGASE; MAMMALIAN-CELLS; MESSENGER-RNA; DISLOCATION; MECHANISM; SITE; PLATFORM Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/67833