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)
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: |
https://repository.cshl.edu/id/eprint/26139 |
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