Mutations in the deubiquitinase gene USP8 cause Cushing's disease

@article{Reincke2015MutationsIT,
  title={Mutations in the deubiquitinase gene USP8 cause Cushing's disease},
  author={Martin Reincke and Silviu Sbiera and Akira Hayakawa and Marily Theodoropoulou and Andrea Osswald and Felix Beuschlein and Thomas Meitinger and Emi Mizuno-Yamasaki and Kohei Kawaguchi and Yasushi Saeki and Kotoko Tanaka and Thomas S Wieland and Elisabeth Graf and Wolfgang Saeger and Cristina L Ronchi and Wim Van Biesen and Michael Buchfelder and Tim Matthias Strom and Martin Fassnacht and Masayuki Komada},
  journal={Nature Genetics},
  year={2015},
  volume={47},
  pages={31-38}
}
Cushing's disease is caused by corticotroph adenomas of the pituitary. To explore the molecular mechanisms of endocrine autonomy in these tumors, we performed exome sequencing of 10 corticotroph adenomas. We found somatic mutations in the USP8 deubiquitinase gene in 4 of 10 adenomas. The mutations clustered in the 14-3-3 protein binding motif and enhanced the proteolytic cleavage and catalytic activity of USP8. Cleavage of USP8 led to increased deubiqutination of the EGF receptor, impairing its… CONTINUE READING
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