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

The EMBO Journal
C ByrdA Varshavsky

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 (t1/2 approximately 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 ...Continue Reading

References

Jan 1, 1992·Annual Review of Genetics·S Jentsch
Jan 2, 1992·Gene·T W ChristiansonP Hieter
Oct 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·R J de GrootJ H Strauss
May 25, 1990·Nucleic Acids Research·M E SchmittB L Trumpower
Mar 24, 1989·Cell·A Bachmair, A Varshavsky
Dec 1, 1995·Genes & Development·R L SmithA D Johnson
Jul 21, 1995·The Journal of Biological Chemistry·E S JohnsonA Varshavsky
Jul 28, 1995·The Journal of Biological Chemistry·R J DohmenA Varshavsky
May 19, 1995·The Journal of Biological Chemistry·R T Baker, A Varshavsky
Sep 2, 1994·Science·K Madura, A Varshavsky
Feb 1, 1996·Current Opinion in Structural Biology·C Wolberger
Mar 1, 1996·Trends in Biochemical Sciences·W Hilt, D H Wolf
Oct 29, 1996·Proceedings of the National Academy of Sciences of the United States of America·A Varshavsky
Dec 6, 1996·Science·R W KingM W Kirschner
Jan 1, 1996·Annual Review of Genetics·M Hochstrasser

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Citations

May 4, 2005·Histochemistry and Cell Biology·Andre Tomasino, Lars Klimaschewski
Jun 11, 2005·Molecular and Cellular Neurosciences·Pujan KavakebiLars Klimaschewski
Oct 3, 2003·Ageing Research Reviews·Kristina Lindsten, Nico P Dantuma
Oct 22, 2011·Nature Reviews. Molecular Cell Biology·Shashikanth M SriramYong Tae Kwon
Jun 7, 2000·The Biochemical Journal·E Rojo-NiersbachN Lehming
Jul 31, 1998·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·C SchauberK Madura
Jan 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jarrod W HeckRandolph Y Hampton
Jun 21, 2008·The Journal of Biological Chemistry·Zanxian XiaAlexander Varshavsky
Aug 19, 2008·The Journal of Biological Chemistry·Alexander Varshavsky
May 14, 2010·Molecular Biology of the Cell·Nadinath B NillegodaAvrom J Caplan
Aug 2, 2005·Molecular and Cellular Biology·Takafumi TasakiYong Tae Kwon
Jun 8, 2001·Annual Review of Biochemistry·C M Pickart
Jan 24, 2006·PLoS Genetics·Oliver R HomannSusan L Lindquist
Mar 16, 2012·Genetics·Per O Ljungdahl, Bertrand Daignan-Fornier
Oct 23, 2002·Proceedings of the National Academy of Sciences of the United States of America·Fangyong DuAlexander Varshavsky
Feb 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·Y Xie, A Varshavsky
Apr 25, 2012·Annual Review of Biochemistry·Takafumi TasakiYong Tae Kwon
Jul 8, 1998·Proceedings of the National Academy of Sciences of the United States of America·Y T KwonA Varshavsky
Oct 15, 1998·Proceedings of the National Academy of Sciences of the United States of America·V SolomonA L Goldberg
Jun 19, 2001·Medicinal Research Reviews·J MyungC M Crews
Sep 14, 2004·Leukemia & Lymphoma·Megan S Lim, Kojo S J Elenitoba-Johnson
Oct 27, 2007·Trends in Biochemical Sciences·Takafumi Tasaki, Yong Tae Kwon
Oct 6, 2015·Trends in Pharmacological Sciences·Jung Hoon LeeMin Jae Lee
Feb 13, 2008·Cellular Microbiology·Katherine E WickliffeMahtab Moayeri
Jun 3, 2011·Protein Science : a Publication of the Protein Society·Alexander Varshavsky

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