A signalling pathway controlling c-Myc degradation that impacts oncogenic transformation of human cells

@article{Yeh2004ASP,
  title={A signalling pathway controlling c-Myc degradation that impacts oncogenic transformation of human cells},
  author={Elizabeth S. Yeh and Michael A. Cunningham and H. J. P. Arnold and Dawn A. D. Chasse and Teresa Monteith and Giovanni Paolo Ivaldi and William C. Hahn and P. Todd Stukenberg and Shirish S Shenolikar and Takafumi Uchida and Christopher M. Counter and J. R. Nevins and Anthony R. Means and Rosalie Sears},
  journal={Nature Cell Biology},
  year={2004},
  volume={6},
  pages={308-318}
}
The stability of c-Myc is regulated by multiple Ras effector pathways. Phosphorylation at Ser 62 stabilizes c-Myc, whereas subsequent phosphorylation at Thr 58 is required for its degradation. Here we show that Ser 62 is dephosphorylated by protein phosphatase 2A (PP2A) before ubiquitination of c-Myc, and that PP2A activity is regulated by the Pin1 prolyl isomerase. Furthermore, the absence of Pin1 or inhibition of PP2A stabilizes c-Myc. A stable c-MycT58A mutant that cannot bind Pin1 or be… CONTINUE READING
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