Implication of the ubiquitin/proteasome system in Myc-regulated transcription

Cell Cycle. 2003 Sep-Oct;2(5):403-7.

Abstract

The c-Myc oncoprotein is a transcription factor that controls genes involved in cell growth, apoptosis and oncogenesis. We and others recently showed that the F-box protein Skp2 interacts with c-Myc and participates in its ubiquitylation and proteasomal degradation. Surprisingly, Skp2 was also found to act as a positive cofactor for c-Myc-regulated transcription. Further, Skp2, ubiquitylated proteins and subunits of the proteasome were demonstrated to be associated with a c-Myc target promoter in vivo. We show here that c-Myc interacts with Skp2 as part of the SCFSkp2 E3 ubiquitin ligase complex. Further, c-Myc interacts with the Sug1, an AAA ATPase subunit of the 19S regulatory particle of the proteasome. Inhibition of Sug1 expression by siRNA reduced transcription from a Myc target promoter to the same extent as c-Myc or Skp2 siRNA, implicating Sug1in this process. Taken together these findings suggest a role of the ubiquitin/proteasome system in c-Myc-regulated transcription. A hypothetical model discussing the link between ubiquitylation and transcription will be presented.

Publication types

  • Review

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Adaptor Proteins, Signal Transducing*
  • Animals
  • COS Cells
  • Carrier Proteins / metabolism
  • Cell Division / physiology
  • Chlorocebus aethiops
  • Cysteine Endopeptidases / metabolism*
  • Intracellular Signaling Peptides and Proteins
  • LIM Domain Proteins
  • Multienzyme Complexes / metabolism*
  • Promoter Regions, Genetic / physiology
  • Proteasome Endopeptidase Complex
  • Protein Interaction Mapping
  • Proto-Oncogene Proteins c-myc / metabolism*
  • S-Phase Kinase-Associated Proteins / metabolism*
  • SKP Cullin F-Box Protein Ligases / metabolism
  • Transcription Factors*
  • Transcription, Genetic / genetics*
  • Transcription, Genetic / physiology
  • Ubiquitins / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • LIM Domain Proteins
  • Multienzyme Complexes
  • PSMC5 protein, human
  • Proto-Oncogene Proteins c-myc
  • S-Phase Kinase-Associated Proteins
  • SUG1 protein, mammalian
  • Transcription Factors
  • Ubiquitins
  • SKP Cullin F-Box Protein Ligases
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • ATPases Associated with Diverse Cellular Activities