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

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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, COS Cells, Carrier Proteins, Cell Division, Cercopithecus aethiops, Cysteine Endopeptidases, LIM Domain Proteins, Multienzyme Complexes, Promoter Regions, Genetic, Proteasome Endopeptidase Complex, Protein Interaction Mapping, Proto-Oncogene Proteins c-myc, S-Phase Kinase-Associated Proteins, SKP Cullin F-Box Protein Ligases, Transcription Factors, Transcription, Genetic, Ubiquitins
Cell Cycle
Date: Sep. 10, 2003
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