A Varshavsky

Summary

Affiliation: California Institute of Technology
Country: USA

Publications

  1. ncbi request reprint Bivalent inhibitor of the N-end rule pathway
    Y T Kwon
    Division of Biology, California Institute of Technology, Pasadena, California 91125, USA
    J Biol Chem 274:18135-9. 1999
  2. pmc The E2-E3 interaction in the N-end rule pathway: the RING-H2 finger of E3 is required for the synthesis of multiubiquitin chain
    Y Xie
    Division of Biology, 147 75, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA
    EMBO J 18:6832-44. 1999
  3. pmc The N-end rule: functions, mysteries, uses
    A Varshavsky
    Division of Biology, California Institute of Technology, Pasadena 91125, USA
    Proc Natl Acad Sci U S A 93:12142-9. 1996
  4. ncbi request reprint A mouse amidase specific for N-terminal asparagine. The gene, the enzyme, and their function in the N-end rule pathway
    S Grigoryev
    Division of Biology, California Institute of Technology, Pasadena, California 91125, USA
    J Biol Chem 271:28521-32. 1996
  5. ncbi request reprint The N-end rule pathway of protein degradation
    A Varshavsky
    Division of Biology, California Institute of Technology, Pasadena 91125, USA
    Genes Cells 2:13-28. 1997
  6. ncbi request reprint Degradation of a cohesin subunit by the N-end rule pathway is essential for chromosome stability
    H Rao
    Division of Biology, California Institute of Technology, Pasadena, California 91125, USA
    Nature 410:955-9. 2001
  7. ncbi request reprint Peptides accelerate their uptake by activating a ubiquitin-dependent proteolytic pathway
    G C Turner
    Division of Biology, California Institute of Technology, Pasadena 91125, USA
    Nature 405:579-83. 2000
  8. ncbi request reprint Detecting and measuring cotranslational protein degradation in vivo
    G C Turner
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Science 289:2117-20. 2000
  9. ncbi request reprint A proteolytic pathway that recognizes ubiquitin as a degradation signal
    E S Johnson
    Division of Biology, California Institute of Technology, Pasadena 91125, USA
    J Biol Chem 270:17442-56. 1995
  10. pmc The mouse and human genes encoding the recognition component of the N-end rule pathway
    Y T Kwon
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Proc Natl Acad Sci U S A 95:7898-903. 1998

Collaborators

Detail Information

Publications43

  1. ncbi request reprint Bivalent inhibitor of the N-end rule pathway
    Y T Kwon
    Division of Biology, California Institute of Technology, Pasadena, California 91125, USA
    J Biol Chem 274:18135-9. 1999
    ..In addition to demonstrating spatial proximity between the type 1 and type 2 substrate-binding sites of Ubr1p, these results provide a route to high affinity inhibitors of the N-end rule pathway...
  2. pmc The E2-E3 interaction in the N-end rule pathway: the RING-H2 finger of E3 is required for the synthesis of multiubiquitin chain
    Y Xie
    Division of Biology, 147 75, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA
    EMBO J 18:6832-44. 1999
    ..These results defined the topography of the Ubc2p-Ubr1p interaction and revealed the essential function of the RING-H2 finger, a domain that is present in many otherwise dissimilar E3 proteins of the ubiquitin system...
  3. pmc The N-end rule: functions, mysteries, uses
    A Varshavsky
    Division of Biology, California Institute of Technology, Pasadena 91125, USA
    Proc Natl Acad Sci U S A 93:12142-9. 1996
    ..In eukaryotes, the N-end rule pathway is a part of the ubiquitin system. I discuss the mechanisms and functions of this pathway, and consider its applications...
  4. ncbi request reprint A mouse amidase specific for N-terminal asparagine. The gene, the enzyme, and their function in the N-end rule pathway
    S Grigoryev
    Division of Biology, California Institute of Technology, Pasadena, California 91125, USA
    J Biol Chem 271:28521-32. 1996
    ..Further dissection of mouse Ntan1, including its null phenotype analysis, should illuminate the functions of the N-end rule, most of which are still unknown...
  5. ncbi request reprint The N-end rule pathway of protein degradation
    A Varshavsky
    Division of Biology, California Institute of Technology, Pasadena 91125, USA
    Genes Cells 2:13-28. 1997
    ..Ubiquitin is a 76-residue protein whose covalent conjugation to other proteins plays a role in many biological processes, including cell growth and differentiation. I discuss the current understanding of the N-end rule pathway...
  6. ncbi request reprint Degradation of a cohesin subunit by the N-end rule pathway is essential for chromosome stability
    H Rao
    Division of Biology, California Institute of Technology, Pasadena, California 91125, USA
    Nature 410:955-9. 2001
    ..A number of yeast proteins bear putative cleavage sites for the ESP1 separin, suggesting other physiological substrates and functions of the N-end rule pathway...
  7. ncbi request reprint Peptides accelerate their uptake by activating a ubiquitin-dependent proteolytic pathway
    G C Turner
    Division of Biology, California Institute of Technology, Pasadena 91125, USA
    Nature 405:579-83. 2000
    ..These findings identify the physiological rationale for the targeting of Cup9 by Ubr1, and indicate that small compounds may regulate other ubiquitin-dependent pathways...
  8. ncbi request reprint Detecting and measuring cotranslational protein degradation in vivo
    G C Turner
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Science 289:2117-20. 2000
    ..Thus, the folding of nascent proteins, including abnormal ones, may be in kinetic competition with pathways that target these proteins for degradation cotranslationally...
  9. ncbi request reprint A proteolytic pathway that recognizes ubiquitin as a degradation signal
    E S Johnson
    Division of Biology, California Institute of Technology, Pasadena 91125, USA
    J Biol Chem 270:17442-56. 1995
    ....
  10. pmc The mouse and human genes encoding the recognition component of the N-end rule pathway
    Y T Kwon
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Proc Natl Acad Sci U S A 95:7898-903. 1998
    ..The cloning of Ubr1 makes possible the construction of Ubr1-lacking mouse strains, a prerequisite for the functional understanding of the mammalian N-end rule pathway...
  11. pmc Physical association of ubiquitin ligases and the 26S proteasome
    Y Xie
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Proc Natl Acad Sci U S A 97:2497-502. 2000
    ..These and related results suggest that a substrate-bound Ub ligase participates in the delivery of substrates to the proteasome, because of affinity between the ligase's E3 component and specific proteins of the 19S particle...
  12. pmc RPN4 is a ligand, substrate, and transcriptional regulator of the 26S proteasome: a negative feedback circuit
    Y Xie
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Proc Natl Acad Sci U S A 98:3056-61. 2001
    ....
  13. ncbi request reprint Yeast N-terminal amidase. A new enzyme and component of the N-end rule pathway
    R T Baker
    Division of Biology, California Institute of Technology, Pasadena 91125, USA
    J Biol Chem 270:12065-74. 1995
    ..The effects of overexpressing Nt-amidase and other components of the N-end rule pathway suggest interactions between these components and the existence of a multienzyme targeting complex...
  14. pmc Altered activity, social behavior, and spatial memory in mice lacking the NTAN1p amidase and the asparagine branch of the N-end rule pathway
    Y T Kwon
    Division of Biology, California Institute of Technology, Pasadena, California 91125, USA
    Mol Cell Biol 20:4135-48. 2000
    ....
  15. pmc Construction and analysis of mouse strains lacking the ubiquitin ligase UBR1 (E3alpha) of the N-end rule pathway
    Y T Kwon
    Division of Biology, California Institute of Technology, Pasadena, California 91125, USA
    Mol Cell Biol 21:8007-21. 2001
    ..We consider these UBR1-like proteins and discuss the functions of the mammalian N-end rule pathway...
  16. pmc The N-end rule pathway controls the import of peptides through degradation of a transcriptional repressor
    C Byrd
    Division of Biology, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA
    EMBO J 17:269-77. 1998
    ..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...
  17. ncbi request reprint N-recognin/Ubc2 interactions in the N-end rule pathway
    K Madura
    Division of Biology, California Institute of Technology, Pasadena 91125
    J Biol Chem 268:12046-54. 1993
    ..The N-recognin.Ubc2 complex appears to regulate the expression of N-recognin through changes in the metabolic stability of its mRNA...
  18. pmc Cdc48p interacts with Ufd3p, a WD repeat protein required for ubiquitin-mediated proteolysis in Saccharomyces cerevisiae
    M Ghislain
    Division of Biology, California Institute of Technology, Pasadena 91125, USA
    EMBO J 15:4884-99. 1996
    ..The discovery of the Ufd3p--Cdc48p complex and the finding that this complex is a part of the Ub system open up a new direction for studies of the function of Ub in the cell cycle and membrane dynamics...
  19. ncbi request reprint A yeast protein similar to bacterial two-component regulators
    I M Ota
    Division of Biology, California Institute of Technology, Pasadena 91125
    Science 262:566-9. 1993
    ..The finding of SLN1 demonstrates that a mode of signal transduction similar to the bacterial two-component design operates in eukaryotes as well...
  20. ncbi request reprint The N-end rule pathway is required for import of histidine in yeast lacking the kinesin-like protein Cin8p
    Y Xie
    Division of Biology, 147 75, Caltech, 1200 East California Blvd, Pasadena, CA 91125, USA
    Curr Genet 36:113-23. 1999
    ..cerevisiae auxotrophic for histidine. We consider possible mechanisms of this previously unsuspected link between kinesins, ubiquitin-dependent proteolysis, and the import of histidine...
  21. pmc Alternative splicing results in differential expression, activity, and localization of the two forms of arginyl-tRNA-protein transferase, a component of the N-end rule pathway
    Y T Kwon
    Division of Biology, California Institute of Technology, Pasadena, California 91125, USA
    Mol Cell Biol 19:182-93. 1999
    ..1 in the skeletal muscle, approximately 0.25 in the spleen, approximately 3.3 in the liver and brain, and approximately 10 in the testis, suggesting that the two R-transferases are functionally distinct...
  22. ncbi request reprint The ubiquitin system
    A Varshavsky
    Division of Biology, California Institute of Technology, Pasadena 91125, USA
    Trends Biochem Sci 22:383-7. 1997
    ..Pathways that involve ubiquitin underlie a multitude of processes, including cell differentiation, the cell cycle and responses to stress...
  23. ncbi request reprint Felix Hoppe-Seyler Lecture 2000. The ubiquitin system and the N-end rule pathway
    A Varshavsky
    Division of Biology, California Institute of Technology, Pasadena 91125, USA
    Biol Chem 381:779-89. 2000
    ....
  24. ncbi request reprint Ubiquitin-specific proteases of Saccharomyces cerevisiae. Cloning of UBP2 and UBP3, and functional analysis of the UBP gene family
    R T Baker
    Division of Biology, California Institute of Technology, Pasadena 91125
    J Biol Chem 267:23364-75. 1992
    ..coli. Null yuh1 ubp1 ubp2 ubp3 quadruple mutants are viable and retain the ability to deubiquitinate ubiquitin fusions, indicating the presence of at least one more ubiquitin-specific processing protease in S. cerevisiae...
  25. ncbi request reprint Cloning and functional analysis of the arginyl-tRNA-protein transferase gene ATE1 of Saccharomyces cerevisiae
    E Balzi
    Laboratoire d Enzymologie, Universite Catholique de Louvain, Belgium
    J Biol Chem 265:7464-71. 1990
    ..Null ate1 mutants are viable but lack the Arg-transferase activity and are unable to degrade those substrates of the N-end rule pathway that start with residues recognized by the Arg-transferase...
  26. ncbi request reprint In vivo degradation of a transcriptional regulator: the yeast alpha 2 repressor
    M Hochstrasser
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139
    Cell 61:697-708. 1990
    ..This subunit-specific degradation makes possible a novel type of posttranslational remodeling in which a heteromeric protein could be functionally modified by selective, degradation-mediated replacement of its subunits...
  27. pmc UBA 1: an essential yeast gene encoding ubiquitin-activating enzyme
    J P McGrath
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139
    EMBO J 10:227-36. 1991
    ..Deletion of the UBA1 gene is lethal, demonstrating that the formation of ubiquitin--protein conjugates is essential for cell viability...
  28. ncbi request reprint The N-end rule in bacteria
    J W Tobias
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139
    Science 254:1374-7. 1991
    ..The adenosine triphosphate-dependent protease Clp (Ti) is required for the degradation of N-end rule substrates in E. coli...
  29. pmc The N-end rule is mediated by the UBC2(RAD6) ubiquitin-conjugating enzyme
    R J Dohmen
    Department of Biology, Massachusettes Institute of Technology, Cambridge 02139
    Proc Natl Acad Sci U S A 88:7351-5. 1991
    ..These results indicate that some of the UBC2 functions, which include DNA repair, induced mutagenesis, sporulation, and regulation of retrotransposition, are mediated by protein degradation via the N-end rule pathway...
  30. ncbi request reprint An essential yeast gene encoding a homolog of ubiquitin-activating enzyme
    R J Dohmen
    Institute für Mikrobiologie, Heinrich Heine Universitat Dusseldorf, Germany
    J Biol Chem 270:18099-109. 1995
    ..Uba2p is multiubiquitinated in vivo, suggesting that at least a fraction of Uba2p is metabolically unstable. Uba2p is likely to be a component of the Ub system that functions as either an E2 or E1/E2 enzyme...
  31. pmc A DNA binding protein that recognizes oligo(dA).oligo(dT) tracts
    E Winter
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139
    EMBO J 8:1867-77. 1989
    ..Null mutants in the DAT gene are viable but phenotypically distinguishable from congenic wild-type strains. We discuss unusual structural features and biochemical properties of datin in relation to its possible functions...
  32. ncbi request reprint Ump1p is required for proper maturation of the 20S proteasome and becomes its substrate upon completion of the assembly
    P C Ramos
    Biotechnologisches Zentrallabor, Institut fur Mikrobiologie, Heinrich Heine Universitat Dusseldorf, Germany
    Cell 92:489-99. 1998
    ..We also show that the propeptide of the Pre2p/Doa3p beta subunit is required for Ump1p's function in proteasome maturation...
  33. pmc The N-end rule in Escherichia coli: cloning and analysis of the leucyl, phenylalanyl-tRNA-protein transferase gene aat
    T E Shrader
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139
    J Bacteriol 175:4364-74. 1993
    ..The aat gene lies downstream of an open reading frame that encodes a homolog of the mammalian multidrug resistance P glycoproteins...
  34. ncbi request reprint The yeast DNA repair gene RAD6 encodes a ubiquitin-conjugating enzyme
    S Jentsch
    Nature 329:131-4. 1987
    ..The discovery that the RAD6 gene product can catalyse the covalent attachment of ubiquitin to other proteins suggests that the multiple functions of the RAD6 protein are mediated by its ubiquitin-conjugating activity...
  35. ncbi request reprint A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein
    V Chau
    Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201
    Science 243:1576-83. 1989
    ..The experiments with ubiquitin mutated at its Lys48 residue indicate that the multiubiquitin chain in a targeted protein is essential for the degradation of the protein...
  36. ncbi request reprint Thermolability of ubiquitin-activating enzyme from the mammalian cell cycle mutant ts85
    D Finley
    Cell 37:43-55. 1984
    ..We discuss possible roles of ubiquitin-dependent pathways in DNA transactions, the cell cycle, and the heat shock response...
  37. pmc Isolation and characterization of DNA sequences amplified in multidrug-resistant hamster cells
    P Gros
    Proc Natl Acad Sci U S A 83:337-41. 1986
    ..Our results strongly suggest that the 5-kb mRNA species plays a role in the mechanism of multidrug resistance common to the LZ and C5 cell lines...
  38. ncbi request reprint Cloning and functional analysis of the ubiquitin-specific protease gene UBP1 of Saccharomyces cerevisiae
    J W Tobias
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139
    J Biol Chem 266:12021-8. 1991
    ..Null ubp1 mutants are viable, and retain the ability to deubiquitinate ubiquitin-beta-galactosidase, indicating that the family of ubiquitin-specific proteases in yeast is not limited to UBP1 and YUH1...
  39. pmc The yeast ubiquitin genes: a family of natural gene fusions
    E Ozkaynak
    EMBO J 6:1429-39. 1987
    ..Elsewhere we show that the essential function of the UB14 gene is to provide ubiquitin to cells under stress...
  40. ncbi request reprint The yeast cell cycle gene CDC34 encodes a ubiquitin-conjugating enzyme
    M G Goebl
    Department of Genetics, University of Washington, Seattle 98195
    Science 241:1331-5. 1988
    ..The cell cycle function of CDC34 is thus likely to be mediated by the ubiquitin-conjugating activity of its product...
  41. pmc Ubiquitin as a degradation signal
    E S Johnson
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139
    EMBO J 11:497-505. 1992
    ..This generally applicable, cis-acting signal can be used to manipulate the in vivo half-lives of specific intracellular proteins...
  42. ncbi request reprint The tails of ubiquitin precursors are ribosomal proteins whose fusion to ubiquitin facilitates ribosome biogenesis
    D Finley
    Department of Cellular and Molecular Physiology, Harvard Medical School, Boston, Massachusetts 02115
    Nature 338:394-401. 1989
    ..These results suggest a novel 'chaperone' function for ubiquitin, in which its covalent association with other proteins promotes the formation of specific cellular structures...
  43. ncbi request reprint Unified nomenclature for subunits of the Saccharomyces cerevisiae proteasome regulatory particle
    D Finley
    Trends Biochem Sci 23:244-5. 1998