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Cold shock Y-box protein-1 proteolysis autoregulates its transcriptional activities van Roeyen, Claudia R; Scurt, Florian G; Brandt, Sabine; Kuhl, Vanessa A; Martinkus, Sandra; Djudjaj, Sonja; Raffetseder, Ute; Royer, Hans-Dieter; Stefanidis, Ioannis; Dunn, Sandra E; Dooley, Steven; Weng, Honglei; Fischer, Thomas; Lindquist, Jonathan A; Mertens, Peter R

Abstract

Background: The Y-box protein-1 (YB-1) fulfills pleiotropic functions relating to gene transcription, mRNA processing, and translation. It remains elusive how YB-1 shuttling into the nuclear and cytoplasmic compartments is regulated and whether limited proteolysis by the 20S proteasome releases fragments with distinct function(s) and subcellular distribution(s). Results: To address these questions, mapping of domains responsible for subcellular targeting was performed. Three nuclear localization signals (NLS) were identified. NLS-1 (aa 149-156) and NLS-2 (aa 185-194) correspond to residues with unknown function(s), whereas NLS-3 (aa 276-292) matches with a designated multimerization domain. Nuclear export signal(s) were not identified. Endoproteolytic processing by the 20S proteasome before glycine 220 releases a carboxy-terminal fragment (CTF), which localized to the nucleus, indicating that NLS-3 is operative. Genotoxic stress induced proteolytic cleavage and nuclear translocation of the CTF. Co-expression of the CTF and full-length YB-1 resulted in an abrogated transcriptional activation of the MMP-2 promoter, indicating an autoregulatory inhibitory loop, whereas it fulfilled similar trans-repressive effects on the collagen type I promoter. Conclusion: Compartmentalization of YB-1 protein derivatives is controlled by distinct NLS, one of which targets a proteolytic cleavage product to the nucleus. We propose a model for an autoregulatory negative feedback loop that halts unlimited transcriptional activation.

Item Metadata

Title
Cold shock Y-box protein-1 proteolysis autoregulates its transcriptional activities
Creator
van Roeyen, Claudia R; Scurt, Florian G; Brandt, Sabine; Kuhl, Vanessa A; Martinkus, Sandra; Djudjaj, Sonja; Raffetseder, Ute; Royer, Hans-Dieter; Stefanidis, Ioannis; Dunn, Sandra E; Dooley, Steven; Weng, Honglei; Fischer, Thomas; Lindquist, Jonathan A; Mertens, Peter R
Contributor
Child and Family Research Institute
Publisher
BioMed Central
Date Issued
2013-08-27
Description
Background: The Y-box protein-1 (YB-1) fulfills pleiotropic functions relating to gene transcription, mRNA processing, and translation. It remains elusive how YB-1 shuttling into the nuclear and cytoplasmic compartments is regulated and whether limited proteolysis by the 20S proteasome releases fragments with distinct function(s) and subcellular distribution(s). Results: To address these questions, mapping of domains responsible for subcellular targeting was performed. Three nuclear localization signals (NLS) were identified. NLS-1 (aa 149-156) and NLS-2 (aa 185-194) correspond to residues with unknown function(s), whereas NLS-3 (aa 276-292) matches with a designated multimerization domain. Nuclear export signal(s) were not identified. Endoproteolytic processing by the 20S proteasome before glycine 220 releases a carboxy-terminal fragment (CTF), which localized to the nucleus, indicating that NLS-3 is operative. Genotoxic stress induced proteolytic cleavage and nuclear translocation of the CTF. Co-expression of the CTF and full-length YB-1 resulted in an abrogated transcriptional activation of the MMP-2 promoter, indicating an autoregulatory inhibitory loop, whereas it fulfilled similar trans-repressive effects on the collagen type I promoter. Conclusion: Compartmentalization of YB-1 protein derivatives is controlled by distinct NLS, one of which targets a proteolytic cleavage product to the nucleus. We propose a model for an autoregulatory negative feedback loop that halts unlimited transcriptional activation.
Subject
Cold shock protein; DbpB; YBX1; Nuclear localization signal; Post-translational modification; RNA/DNA binding protein
Genre
Article
Type
Text
Language
eng
Date Available
2016-01-19
Provider
Vancouver : University of British Columbia Library
Rights
Attribution 4.0 International (CC BY 4.0)
DOI
10.14288/1.0223555
URI
http://hdl.handle.net/2429/56616
Affiliation
Medicine, Faculty of; Pediatrics, Department of
Citation
Cell Communication and Signaling. 2013 Aug 27;11(1):63
Publisher DOI
10.1186/1478-811X-11-63
Peer Review Status
Reviewed
Scholarly Level
Faculty
Copyright Holder
van Roeyen et al.; licensee BioMed Central Ltd.
Rights URI
http://creativecommons.org/licenses/by/4.0/
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Attribution 4.0 International (CC BY 4.0)