Ubiquitylation of the amino terminus of Myc by SCF(β-TrCP) antagonizes SCF(Fbw7)-mediated turnover.
The SCFFbw7 ubiquitin ligase mediates growth-factor-regulated turnover of the Myc oncoprotein. Here we show that SCFβ-TrCP binds to Myc by means of a characteristic phosphodegron and ubiquitylates Myc; this results in enhanced Myc stability. SCFFbw7 and SCFβ-TrCP can exert these differential effects through polyubiquitylation of the amino terminus of Myc. ... Whereas SCFFbw7 with the Cdc34 ubiquitin-conjugating enzyme specifically requires lysine 48 (K48) of ubiquitin, SCFβ-TrCP uses the UbcH5 ubiquitin-conjugating enzyme to form heterotypic polyubiquitin chains on Myc. Ubiquitylation of Myc by SCFβ-TrCP is required for Myc-dependent acceleration of cell cycle progression after release from an arrest in S phase. Therefore, alternative ubiquitylation events at the N terminus can lead to the ubiquitylation-dependent stabilization of Myc.
Mesh Terms:
Amino Acid Motifs, Animals, Cell Cycle Proteins, Cells, Cultured, Consensus Sequence, F-Box Proteins, G2 Phase, Hela Cells, Humans, Mice, Models, Biological, NIH 3T3 Cells, Polyubiquitin, Protein Binding, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-myc, S Phase, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligase Complexes, Ubiquitin-Protein Ligases, Ubiquitination, beta-Transducin Repeat-Containing Proteins
Amino Acid Motifs, Animals, Cell Cycle Proteins, Cells, Cultured, Consensus Sequence, F-Box Proteins, G2 Phase, Hela Cells, Humans, Mice, Models, Biological, NIH 3T3 Cells, Polyubiquitin, Protein Binding, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-myc, S Phase, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligase Complexes, Ubiquitin-Protein Ligases, Ubiquitination, beta-Transducin Repeat-Containing Proteins
Nat. Cell Biol.
Date: Oct. 01, 2010
PubMed ID: 20852628
View in: Pubmed Google Scholar
Download Curated Data For This Publication
119019
Switch View:
- Interactions 3