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 Melissa 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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