C. Byrd et al., THE N-END RULE PATHWAY CONTROLS THE IMPORT OF PEPTIDES THROUGH DEGRADATION OF A TRANSCRIPTIONAL REPRESSOR, EMBO journal, 17(1), 1998, pp. 269-277
Ubiquitin-dependent proteolytic systems underlie many processes, inclu
ding 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 mai
n recognition component of this pathway, regulates peptide import in t
he yeast Saccharomyces cerevisiae through degradation of Cup9p, a 35 k
Da homeodomain protein, Cup9p was identified using a screen for mutant
s that bypass the previously observed requirement for Ubr1p in peptide
import, We show that Cup9p is a short-lived protein (t(1/2) Alpha sim
ilar to 5 min) whose degradation requires Ubr1p, Cup9p acts as a repre
ssor of PTR2, a gene encoding the transmembrane peptide transporter. I
n contrast to engineered N-end rule substrates, which are recognized b
y Ubr1p through their destabilizing N-terminal residues, Cup9p is targ
eted by Ubr1p through an internal degradation signal. The Ubr1p-Cup9p-
Ptr2p circuit is the first example of a physiological process controll
ed by the N-end rule pathway, An earlier study identified Cup9p as a p
rotein required for an aspect of resistance to copper toxicity in S. c
erevisiae. Thus, one physiological substrate of the N-end rule pathway
functions as both a repressor of peptide import and a regulator of co
pper homeostasis.