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The F-Box Protein Skp2 Participates in c-Myc Proteosomal Degradation and Acts as a Cofactor for c-Myc-Regulated Transcription

von der Lehr, Natalie, Johansson, Sara, Wu, Siqin, Bahram, Fuad, Castell, Alina, Cetinkaya, Cihan, Hydbring, Per, Weidung, Ingrid, Nakayama, Keiko, Nakayama, Keiichi I, Söderberg, Ola, Kerppola, Tom K, Larsson, Lars-Gunnar·2003·Molecular Cell
DOI 10.1016/s1097-2765(03)00193-x
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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.

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Citations

Cites

Research works printed but not linked: 38

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Cited by

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Metadata

Authors
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.
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2003-05
Volume
11
Issue
5
Pages
1189-1200
ISSN
1097-2765
DOI
10.1016/s1097-2765(03)00193-x
Cited by
408
References
3
Language
en
Licence

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