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Cell Commun Signal. 2013 Aug 27;11:63. doi: 10.1186/1478-811X-11-63.

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

Author information

1
Department of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke University Magdeburg, Leipziger Str 44, 39120 Magdeburg, Germany. peter.mertens@med.ovgu.de.

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.

PMID:
24103640
PMCID:
PMC3766096
DOI:
10.1186/1478-811X-11-63
[Indexed for MEDLINE]
Free PMC Article
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