Universität zu Köln

Poulsen, Esben G., Kampmeyer, Caroline, Kriegenburg, Franziska, Johansen, Jens V., Hofmann, Kay ORCID: 0000-0002-2289-9083, Holmberg, Christian ORCID: 0000-0001-9224-0543 and Hartmann-Petersen, Rasmus ORCID: 0000-0002-4155-7791 (2017). UBL/BAG-domain co-chaperones cause cellular stress upon overexpression through constitutive activation of Hsf1. Cell Stress Chaperones, 22 (1). S. 143 - 155. DORDRECHT: SPRINGER. ISSN 1466-1268

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Abstract

As a result of exposure to stress conditions, mutations, or defects during synthesis, cellular proteins are prone to misfold. To cope with such partially denatured proteins, cells mount a regulated transcriptional response involving the Hsf1 transcription factor, which drives the synthesis of molecular chaperones and other stress-relieving proteins. Here, we show that the fission yeast Schizosaccharomyces pombe orthologues of human BAG-1, Bag101, and Bag102, are Hsp70 co-chaperones that associate with 26S proteasomes. Only a subgroup of Hsp70-type chaperones, including Ssa1, Ssa2, and Sks2, binds Bag101 and Bag102 and key residues in the Hsp70 ATPase domains, required for interaction with Bag101 and Bag102, were identified. In humans, BAG-1 overexpression is typically observed in cancers. Overexpression of bag101 and bag102 in fission yeast leads to a strong growth defect caused by triggering Hsp70 to release and activate the Hsf1 transcription factor. Accordingly, the bag101-linked growth defect is alleviated in strains containing a reduced amount of Hsf1 but aggravated in hsp70 deletion strains. In conclusion, we propose that the fission yeast UBL/BAG proteins release Hsf1 from Hsp70, leading to constitutive Hsf1 activation and growth defects.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Poulsen, Esben G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kampmeyer, Caroline UNSPECIFIED UNSPECIFIED UNSPECIFIED Kriegenburg, Franziska UNSPECIFIED UNSPECIFIED UNSPECIFIED Johansen, Jens V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hofmann, Kay UNSPECIFIED orcid.org/0000-0002-2289-9083 UNSPECIFIED Holmberg, Christian UNSPECIFIED orcid.org/0000-0001-9224-0543 UNSPECIFIED Hartmann-Petersen, Rasmus UNSPECIFIED orcid.org/0000-0002-4155-7791 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-248318
DOI:	10.1007/s12192-016-0751-z
Journal or Publication Title:	Cell Stress Chaperones
Volume:	22
Number:	1
Page Range:	S. 143 - 155
Date:	2017
Publisher:	SPRINGER
Place of Publication:	DORDRECHT
ISSN:	1466-1268
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; MOLECULAR CHAPERONES; FISSION YEAST; BAG-1; PROTEASOME; CHIP; COOPERATION; EXPRESSION; DYNAMICS; FAMILY Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/24831