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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Welcker, Markus Orian, Amir Grim, Jonathan E. Clurman, Bruce E. Eisenman, Robert N. Grim, Jonathan A. Jin, Jianping Harper, J. Wade |
| Description | Author Affiliation: Welcker M ( Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.); |
| 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 as c-Myc, the loss of Fbw7 is likely to elicit profound effects on cell proliferation during tumorigenesis. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 24 |
| Volume Number | 101 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2004-06-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cell Cycle Proteins Metabolism F-Box Proteins Glycogen Synthase Kinase 3 Proto-Oncogene Proteins C-myc Tumor Suppressor Proteins Ubiquitin-Protein Ligases Genetics Cell Line Fibroblasts HeLa Cells Phosphorylation Recombinant Proteins Sequence Alignment Transduction, Genetic Transfection Ubiquitin Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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