Ubiquitylation of the amino terminus of Myc by SCFβ-TrCP antagonizes SCFFbw7-mediated turnover

Abstract

SCFFbw7 mediates the ubiquitylation and degradation of Myc. Now, Myc is also shown to be stabilized by ubquitylation through SCFβ-TrCP. During recovery from S phase arrest, SCFβ-TrCP mediates the addition of a polyubiquitin chain on the Myc amino terminus that is functionally distinct from that formed by Fbw7. 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.

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Popov, N., Schülein, C., Jaenicke, L. et al. Ubiquitylation of the amino terminus of Myc by SCF^β-TrCP antagonizes SCF^Fbw7-mediated turnover. Nat Cell Biol 12, 973–981 (2010). https://doi.org/10.1038/ncb2104

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