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.
von der Lehr
Natalie
N
Department of Plant Biology and Forest Genetics, Uppsala Genetic Center, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Johansson
Sara
S
Larsson
Lars-Gunnar
LG
D000074183:ATPases Associated with Diverse Cellular Activities; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D002522:Chlorocebus aethiops; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D009097:Multienzyme Complexes / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000502:physiology; D046988:Proteasome Endopeptidase Complex; D025941:Protein Interaction Mapping; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism*; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000235:genetics* / Q000502:physiology; D014452:Ubiquitins / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D009097:Multienzyme Complexes; C092282:PSMC5 protein, human; D016271:Proto-Oncogene Proteins c-myc; D044786:S-Phase Kinase-Associated Proteins; C106843:SUG1 protein, mammalian; D014157:Transcription Factors; D014452:Ubiquitins; D044843:SKP Cullin F-Box Protein Ligases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D000074183:ATPases Associated with Diverse Cellular Activities