Cell
Volume 74, Issue 2, 30 July 1993, Pages 357-369
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Article
Multiple ubiquitin-conjugating enzymes participate in the in vivo degradation of the yeast MATα2 repressor

https://doi.org/10.1016/0092-8674(93)90426-QGet rights and content

Abstract

Attachment of ubiquitin to proteins is catalyzed by a family of ubiquitin-conjugating (UBC) enzymes. Although these enzymes are essential for many cellular processes, their molecular functions remain unclear because no physiological target has been identified for any of them. Here we show that four UBC proteins (UBC4, UBC5, UBC6, and UBC7) target the yeast MATα2 transcriptional regulator for intracellular degradation by two distinct ubiquitination pathways. UBC6 and UBC7 define one of the pathways and can physically associate. The UBC6UBC7-containing complex targets the Deg1 degradation signal of α2, a conclusion underscored by the finding that UBC6 is encoded by DOA2, a gene previously implicated in Deg1-mediated degradation. These data reveal an unexpected overlap in substrate specificity among diverse UBC enzymes and suggest a combinatorial mechanism of substrate selection in which UBC enzymes partition into multiple ubiquitination complexes.

References (45)

  • C.A. Keleher et al.

    Ssn6-Tup1 is a general repressor of transcription in yeast

    Cell

    (1992)
  • P. Lamb et al.

    Diversity and specificity in transcriptional regulation: the benefits of heterotypic dimerization

    Trends Biochem. Sci.

    (1991)
  • L.M. Mylin et al.

    Regulated GAL4 expression cassette providing controllable and high-level output from high-copy galactose promoters in yeast

    Meth. Enzymol.

    (1990)
  • C.M. Pickart et al.

    Functional heterogeneity of ubiquitin carrier proteins

    J. Biol. Chem.

    (1985)
  • S. Qin et al.

    Cloning and characterization of a Saccharomyces cerevisiae gene encoding a new member of the ubiquitin-conjugating protein family

    J. Biol. Chem.

    (1991)
  • K. Tatchell et al.

    In vitro mutation analysis of the mating-type locus in yeast

    Cell

    (1981)
  • A. Varshavsky

    The N-end rule

    Cell

    (1992)
  • A. Vassal et al.

    QRI8, a novel ubiquitin-conjugating enzyme in Saccharomyces cerevisiae

    Biochem. Biophys. Acta

    (1992)
  • A.S. Zervos et al.

    Mxi1, a protein that specifically interacts with Max to bind Myc-Max recognition sites

    Cell

    (1993)
  • F.M. Ausubel et al.

    Current Protocols in Molecular Biology

    (1989)
  • V. Chau et al.

    A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein

    Science

    (1989)
  • R.J. Dohmen et al.

    The N-end rule is mediated by the UBC2 (RAD6) ubiquitin-conjugating enzyme

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    Present address: Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Strasse 10, O-1115 Berlin-Buch, Federal Republic of Germany.

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