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

Natalie Von Der Lehr, Sara Johansson, Siqin Wu, Fuad Bahram, Alina Castell, Cihan Cetinkaya, Per Hydbring, Ingrid Weidung, Keiko Nakayama, Keiichi I. Nakayama, Ola Söderberg, Tom K. Kerppola, Lars Gunnar Larsson

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364 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1189-1200
Number of pages12
JournalMolecular Cell
Volume11
Issue number5
DOIs
Publication statusPublished - May 1 2003

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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    Von Der Lehr, N., Johansson, S., Wu, S., Bahram, F., Castell, A., Cetinkaya, C., Hydbring, P., Weidung, I., Nakayama, K., Nakayama, K. I., Söderberg, O., Kerppola, T. K., & Larsson, L. G. (2003). The F-box protein Skp2 participates in c-Myc proteosomal degradation and acts as a cofactor for c-Myc-regulated transcription. Molecular Cell, 11(5), 1189-1200. https://doi.org/10.1016/S1097-2765(03)00193-X