The Fbw7 tumor suppressor regulates glycogen synthase kinase 3 phosphorylation-dependent c-Myc protein degradation
Harvard University · University of Washington · +1 more institution
Abstract
Myc proteins regulate cell growth and division and are implicated in a wide range of human cancers. We show here that Fbw7, a component of the SCF(Fbw7) ubiquitin ligase and a tumor suppressor, promotes proteasome-dependent c-Myc turnover in vivo and c-Myc ubiquitination in vitro. Phosphorylation of c-Myc on threonine-58 (T58) by glycogen synthase kinase 3 regulates the binding of Fbw7 to c-Myc as well as Fbw7-mediated c-Myc degradation and ubiquitination. T58 is the most frequent site of c-myc mutations in lymphoma cells, and our findings suggest that c-Myc activation is one of the key oncogenic consequences of Fbw7 loss in cancer. Because Fbw7 mediates the degradation of cyclin E, Notch, and c-Jun, as well…
Citation impact
- FWCI
- 12.05
- Percentile
- 100%
- References
- 49
Authors
7- MWMarkus WelckerCorresponding
Harvard University, University of Washington, Fred Hutch Cancer Center
- AOAmir Orian
Harvard University, University of Washington, Fred Hutch Cancer Center
- JJJianping Jin
Harvard University, University of Washington, Fred Hutch Cancer Center
- JGJonathan Grim
Harvard University, University of Washington, Fred Hutch Cancer Center
- JWJ. Wade Harper
Harvard University, University of Washington, Fred Hutch Cancer Center
Topics & keywords
- Ubiquitin ligase
- F-box protein
- GSK-3
- Ubiquitin
- Biology
- Proteasome
- Ubiquitin-conjugating enzyme
- Carcinogenesis
- Good health and well-being