Universität zu Köln

Turakhiya, Ankit, Meyer, Susanne R., Marincola, Gabriella ORCID: 0000-0001-9227-6554, Boehm, Stefanie, Vanselow, Jens T., Schlosser, Andreas, Hofmann, Kay ORCID: 0000-0002-2289-9083 and Buchberger, Alexander ORCID: 0000-0002-2836-0820 (2018). ZFAND1 Recruits p97 and the 26S Proteasome to Promote the Clearance of Arsenite-Induced Stress Granules. Mol. Cell, 70 (5). S. 906 - 927. CAMBRIDGE: CELL PRESS. ISSN 1097-4164

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Abstract

Stress granules (SGs) are cytoplasmic assemblies of mRNPs stalled in translation initiation. They are induced by various stress conditions, including exposure to the environmental toxin and carcinogen arsenic. While perturbed SG turnover is linked to the pathogenesis of neurodegenerative diseases, the molecular mechanisms underlying SG formation and turnover are still poorly understood. Here, we show that ZFAND1 is an evolutionarily conserved regulator of SG clearance. ZFAND1 interacts with two key factors of protein degradation, the 26S proteasome and the ubiquitin-selective segregase p97, and recruits them to arsenite-induced SGs. In the absence of ZFAND1, SGs lack the 26S proteasome and p97, accumulate defective ribosomal products, and persist after arsenite removal, indicating their transformation into aberrant, disease-linked SGs. Accordingly, ZFAND1 depletion is epistatic to the expression of pathogenic mutant p97 with respect to SG clearance, suggesting that ZFAND1 function is relevant to the multisystem degenerative disorder IBMPFD/ALS.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Turakhiya, Ankit UNSPECIFIED UNSPECIFIED UNSPECIFIED Meyer, Susanne R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Marincola, Gabriella UNSPECIFIED orcid.org/0000-0001-9227-6554 UNSPECIFIED Boehm, Stefanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Vanselow, Jens T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schlosser, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Hofmann, Kay UNSPECIFIED orcid.org/0000-0002-2289-9083 UNSPECIFIED Buchberger, Alexander UNSPECIFIED orcid.org/0000-0002-2836-0820 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-182985
DOI:	10.1016/j.molcel.2018.04.021
Journal or Publication Title:	Mol. Cell
Volume:	70
Number:	5
Page Range:	S. 906 - 927
Date:	2018
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1097-4164
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PROTEIN-QUALITY CONTROL; UBIQUITINATED PROTEINS; VCP DISEASE; AUTOPHAGY; SYSTEM; CELLS; PROTEOTOXICITY; DEGRADATION; CHAPERONE; VCP/P97 Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/18298