Context of multiubiquitin chain attachment influences the rate of Sic1 degradation

Mol Cell. 2003 Jun;11(6):1435-44. doi: 10.1016/s1097-2765(03)00221-1.


The ubiquitin-dependent targeting of proteins to the proteasome is an essential mechanism for regulating eukaryotic protein stability. Here we define the minimal signal for the degradation of the S phase CDK inhibitor Sic1. Of 20 lysines scattered throughout Sic1, 6 N-terminal lysines serve as major ubiquitination sites. Sic1 lacking these lysines (K0N) is stable in vivo, but readdition of any one restores turnover. Nevertheless, ubiquitin chains attached at different N-terminal lysines specify degradation in vitro at markedly different rates. Moreover, although K0N can be ubiquitinated by SCF(Cdc4)/Cdc34 in vitro in the absence (but not in the presence) of S-CDK, it is degraded slowly. Our results reveal that a single multiubiquitin chain can sustain a physiological turnover rate, but that chain position plays an unexpectedly significant role in the rate of proteasomal proteolysis.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cyclin-Dependent Kinase Inhibitor Proteins
  • Enzyme Inhibitors / metabolism*
  • Lysine / genetics
  • Lysine / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Substrate Specificity
  • Ubiquitin / metabolism*


  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor Proteins
  • Enzyme Inhibitors
  • Recombinant Fusion Proteins
  • SIC1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Ubiquitin
  • Lysine