Ubiquitin as a degradation signal

EMBO J. 1992 Feb;11(2):497-505.

Abstract

For many short-lived eukaryotic proteins, conjugation to ubiquitin, yielding a multiubiquitin chain, is an obligatory pre-degradation step. The conjugated ubiquitin moieties function as a 'secondary' signal for degradation, in that their posttranslational coupling to a substrate protein is mediated by amino acid sequences of the substrate that act as a primary degradation signal. We report that the fusion protein ubiquitin--proline--beta-galactosidase (Ub-P-beta gal) is short-lived in the yeast Saccharomyces cerevisiae because its N-terminal ubiquitin moiety functions as an autonomous, primary degradation signal. This signal mediates the formation of a multiubiquitin chain linked to Lys48 of the N-terminal ubiquitin in Ub-P-beta gal. The degradation of Ub-P-beta gal is shown to require Ubc4, one of at least seven ubiquitin-conjugating enzymes in S.cerevisiae. Our findings provide the first direct evidence that a monoubiquitin moiety can function as an autonomous degradation signal. This generally applicable, cis-acting signal can be used to manipulate the in vivo half-lives of specific intracellular proteins.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Kinetics
  • Molecular Sequence Data
  • Mutagenesis, Insertional
  • Oligodeoxyribonucleotides
  • Plasmids
  • Recombinant Fusion Proteins / metabolism
  • Restriction Mapping
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Signal Transduction*
  • Ubiquitins / genetics
  • Ubiquitins / metabolism*
  • beta-Galactosidase / genetics
  • beta-Galactosidase / metabolism

Substances

  • Oligodeoxyribonucleotides
  • Recombinant Fusion Proteins
  • Ubiquitins
  • beta-Galactosidase