Cold shock Y-box protein-1 proteolysis autoregulates its transcriptional activities

Cell Communication and Signaling

Research

Hans-Dieter Royer¹  Thomas Fischer²  Sandra Martinkus³  Claudia RC van Roeyen³  Vanessa A Kuhl³  Ute Raffetseder³  Sabine Brandt⁴  Jonathan A Lindquist⁴  Florian G Scurt⁴  Peter R Mertens⁴  Sonja Djudjaj⁴  Ioannis Stefanidis⁵  Sandra E Dunn⁶  Steven Dooley⁷  Honglei Weng⁷ 

[1] Breast Cancer Research, Center of Advanced European Studies and Research, Caesar, Bonn, Germany;Department of Hematology and Oncology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany;Department of Nephrology and Clinical Immunology, RWTH Aachen University, Aachen, Germany;Department of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke University Magdeburg, Leipziger Str 44, 39120, Magdeburg, Germany;Department of Nephrology, University of Thessaly, Larissa, Greece;Laboratory for Oncogenomic Research, Departments of Pediatrics and Experimental Medicine, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada;Molecular Hepatology, Department of Medicine II, University of Heidelberg, Mannheim, Germany;

关键词: Cold shock protein;    DbpB;    YBX1;    Nuclear localization signal;    Post-translational modification;    RNA/DNA binding protein;   

DOI  :  10.1186/1478-811X-11-63

 received in 2013-02-13, accepted in 2013-08-12,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundThe 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).ResultsTo 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.ConclusionCompartmentalization 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.

【 授权许可】

Unknown   
© van Roeyen et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.