The Fbw7 tumor suppressor regulates glycogen synthase kinase 3 phosphorylation-dependent c-Myc protein degradation
Markus Welcker,Amir Orian,Jianping Jin,Jonathan A. Grim,Jonathan A. Grim,J. Wade Harper,Robert N. Eisenman,Bruce E. Clurman,Bruce E. Clurman +8 more
TLDR
It is shown that Fbw7, a component of the SCFFbw 7 ubiquitin ligase and a tumor suppressor, promotes proteasome-dependent c-Myc turnover in vivo and c- myc ubiquitination in vitro.Abstract:Â
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 SCFFbw7 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 as c-Myc, the loss of Fbw7 is likely to elicit profound effects on cell proliferation during tumorigenesis.read more
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AKT/PKB Signaling: Navigating the Network
Brendan D. Manning,Alex Toker +1 more
TL;DR: Improved understanding of the molecular wiring of the AKT signaling network continues to make an impact that cuts across most disciplines of the biomedical sciences.
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Ubiquitin ligases: cell-cycle control and cancer
TL;DR: A better understanding of the ubiquitylation machinery will provide new insights into the regulatory biology of cell-cycle transitions and the development of anti-cancer drugs.
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Transcriptional regulation and transformation by Myc proteins
Sovana Adhikary,Martin Eilers +1 more
TL;DR: A wealth of data has shed new light on the biochemical functions of Myc proteins and on the mechanisms through which they function in cellular transformation.
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FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiation.
TL;DR: Structural and functional aspects of FBW7, the substrate recognition component of an evolutionary conserved SCF, and its role in the development of cancer are focused on.
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Myc's broad reach.
Martin Eilers,Robert N. Eisenman +1 more
TL;DR: The nature of the genes and pathways that are targeted by Myc, and the role of Myc in stem cell and cancer biology are reviewed.
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Phosphorylation-Dependent Ubiquitination of Cyclin E by the SCFFbw7 Ubiquitin Ligase
Deanna M. Koepp,Laura Schaefer,Xin Ye,Khandan Keyomarsi,Claire Chu,J. Wade Harper,Stephen J. Elledge +6 more
TL;DR: The ubiquitin ligase responsible for cyclin E ubiquitination as SCFFbw7 is identified and it is demonstrated that it is functionally conserved in yeast, flies, and mammals.