The N-end rule pathway controls the import of peptides through degradation of a transcriptional repressor

Byrd, C., Turner, G. C., Varshavsky, A. (1998) The N-end rule pathway controls the import of peptides through degradation of a transcriptional repressor. Embo Journal, 17 (1). pp. 269-277. ISSN 02614189 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/9427760
DOI: 10.1093/emboj/17.1.269

Abstract

Ubiquitin-dependent proteolytic systems underlie many processes, including the cell cycle, cell differentiation and responses to stress. One such system is the N-end rule pathway, which targets proteins bearing destabilizing N-terminal residues. Here we report that Ubr1p, the main recognition component of this pathway, regulates peptide import in the yeast Saccharomyces cerevisiae through degradation of Cup9p, a 35 kDa homeodomain protein. Cup9p was identified using a screen for mutants that bypass the previously observed requirement for Ubr1p in peptide import. We show that Cup9p is a short-lived protein (t( 1/4 ) ~ 5 min) whose degradation requires Ubr1p. Cup9p acts as a repressor of PTR2, a gene encoding the transmembrane peptide transporter. In contrast to engineered N-end rule substrates, which are recognized by Ubr1p through their destabilizing N-terminal residues, Cup9p is targeted by Ubr1p through an internal degradation signal. The Ubr1p-Cup9p-Ptr2p circuit is the first example of a physiological process controlled by the N-end rule pathway. An earlier study identified Cup9p as a protein required for an aspect of resistance to copper toxicity in S.cerevisiae. Thus, one physiological substrate of the N-end rule pathway functions as both a repressor of peptide import and a regulator of copper homeostasis.

Item Type: Paper
Uncontrolled Keywords: CUP9 N-end rule Peptide import Proteolysis PTR2 UBR1 copper homeodomain protein peptide repressor protein amino terminal sequence article controlled study gene targeting homeostasis nonhuman priority journal protein degradation protein transport saccharomyces cerevisiae transcription regulation Biological Transport Carrier Proteins Fungal Proteins Homeodomain Proteins Hydrolysis Ligases Membrane Proteins Membrane Transport Proteins Peptides Recombinant Proteins Repressor Proteins Saccharomyces cerevisiae Proteins Transcription Factors Ubiquitin-Conjugating Enzymes
Subjects: organism description > yeast > Saccharomyces
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein characterization
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > ubiquitin ligase
CSHL Authors:
Communities: CSHL labs > Turner lab
Depositing User: CSHL Librarian
Date: 1998
Date Deposited: 11 Apr 2012 15:36
Last Modified: 14 Mar 2013 16:20
PMCID: PMC1170377
Related URLs:
URI: http://repository.cshl.edu/id/eprint/26139

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