The F-box protein Skp2 participates in c-Myc proteosomal degradation and acts as a cofactor for c-Myc-regulated transcription

Mol Cell. 2003 May;11(5):1189-200. doi: 10.1016/s1097-2765(03)00193-x.


The transcription regulatory oncoprotein c-Myc controls genes involved in cell growth, apoptosis, and oncogenesis. c-Myc is turned over very quickly through the ubiquitin/proteasome pathway. The proteins involved in this process are still unknown. We have found that Skp2 interacts with c-Myc and participates in its ubiquitylation and degradation. The interaction between Skp2 and c-Myc occurs during the G1 to S phase transition of the cell cycle in normal lymphocytes. Surprisingly, Skp2 enhances c-Myc-induced S phase transition and activates c-Myc target genes in a Myc-dependent manner. Further, Myc-induced transcription was shown to be Skp2 dependent, suggesting interdependence between c-Myc and Skp2 in activation of transcription. Moreover, Myc-dependent association of Skp2, ubiquitylated proteins, and subunits of the proteasome to a c-Myc target promoter was demonstrated in vivo. The results suggest that Skp2 is a transcriptional cofactor for c-Myc and indicates a close relationship between transcription activation and transcription factor ubiquitination.

MeSH terms

  • Animals
  • COS Cells
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Division / genetics
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Cyclin D2
  • Cyclins / genetics
  • Cyclins / metabolism
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / metabolism*
  • Eukaryotic Cells / metabolism*
  • Gene Expression Regulation, Neoplastic / genetics
  • Genes, Regulator / genetics*
  • HeLa Cells
  • Humans
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism*
  • Promoter Regions, Genetic / genetics
  • Proteasome Endopeptidase Complex
  • Protein Binding / genetics
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • S Phase / genetics
  • S-Phase Kinase-Associated Proteins
  • Transcriptional Activation / genetics
  • Ubiquitin / genetics
  • Ubiquitin / metabolism


  • CCND2 protein, human
  • Cell Cycle Proteins
  • Cyclin D2
  • Cyclins
  • MYC protein, human
  • Multienzyme Complexes
  • Proto-Oncogene Proteins c-myc
  • S-Phase Kinase-Associated Proteins
  • Ubiquitin
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex