Universität zu Köln

Balaji, Vishnu, Mueller, Leonie, Lorenz, Robin, Kevei, Eva ORCID: 0000-0002-0560-9208, Zhang, William H., Santiago, Ulises, Gebauer, Jan ORCID: 0000-0002-3989-4748, Llamas, Ernesto, Vilchez, David, Camacho, Carlos J., Pokrzywa, Wojciech and Hoppe, Thorsten (2022). A dimer-monomer switch controls CHIP-dependent substrate ubiquitylation and processing. Mol. Cell, 82 (17). S. 3239 - 3267. CAMBRIDGE: CELL PRESS. ISSN 1097-4164

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Abstract

The high substrate selectivity of the ubiquitin/proteasome system is mediated by a large group of E3 ubiquitin ligases. The ubiquitin ligase CHIP regulates the degradation of chaperone-controlled and chaperone -inde-pendent proteins. To understand how CHIP mediates substrate selection and processing, we performed a structure-function analysis of CHIP and addressed its physiological role in Caenorhabditis elegans and hu-man cells. The conserved function of CHIP in chaperone-assisted degradation requires dimer formation to mediate proteotoxic stress resistance and to prevent protein aggregation. The CHIP monomer, however, promotes the turnover of the membrane-bound insulin receptor and longevity. The dimer-monomer transition is regulated by CHIP autoubiquitylation and chaperone binding, which provides a feedback loop that controls CHIP activity in response to cellular stress. Because CHIP also binds other E3 ligases, such as Parkin, the molecular switch mechanism described here could be a general concept for the regulation of substrate selec-tivity and ubiquitylation by combining different E3s.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Balaji, Vishnu UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Leonie UNSPECIFIED UNSPECIFIED UNSPECIFIED Lorenz, Robin UNSPECIFIED UNSPECIFIED UNSPECIFIED Kevei, Eva UNSPECIFIED orcid.org/0000-0002-0560-9208 UNSPECIFIED Zhang, William H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Santiago, Ulises UNSPECIFIED UNSPECIFIED UNSPECIFIED Gebauer, Jan UNSPECIFIED orcid.org/0000-0002-3989-4748 UNSPECIFIED Llamas, Ernesto UNSPECIFIED UNSPECIFIED UNSPECIFIED Vilchez, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Camacho, Carlos J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pokrzywa, Wojciech UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoppe, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-686833
DOI:	10.1016/j.molcel.2022.08.003
Journal or Publication Title:	Mol. Cell
Volume:	82
Number:	17
Page Range:	S. 3239 - 3267
Date:	2022
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1097-4164
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language E3 UBIQUITIN LIGASE; PROTEIN-QUALITY-CONTROL; CAENORHABDITIS-ELEGANS; STRUCTURAL INSIGHTS; CHAPERONE; LONGEVITY; ENZYMES; DAF-16; IDENTIFICATION; DEGRADATION Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68683