Proteolysis of MOB1 by the ubiquitin ligase praja2 attenuates Hippo signalling and supports glioblastoma growth

Luca Lignitto, Antonietta Arcella, Maria Sepe, Laura Rinaldi, Rossella Delle Donne, Adriana Gallo, Eduard Stefan, Verena A. Bachmann, Maria A. Oliva, Clelia Tiziana Storlazzi, Alberto L'Abbate, Arturo Brunetti, Sara Gargiulo, Matteo Gramanzini, Luigi Insabato, Corrado Garbi, Max E. Gottesman, Antonio Feliciello

Research output: Contribution to journalArticlepeer-review


Human glioblastoma is the most frequent and aggressive form of brain tumour in the adult population. Proteolytic turnover of tumour suppressors by the ubiquitin-proteasome system is a mechanism that tumour cells can adopt to sustain their growth and invasiveness. However, the identity of ubiquitin-proteasome targets and regulators in glioblastoma are still unknown. Here we report that the RING ligase praja2 ubiquitylates and degrades Mob, a core component of NDR/LATS kinase and a positive regulator of the tumour-suppressor Hippo cascade. Degradation of Mob through the ubiquitin-proteasome system attenuates the Hippo cascade and sustains glioblastoma growth in vivo. Accordingly, accumulation of praja2 during the transition from low- to high-grade glioma is associated with significant downregulation of the Hippo pathway. These findings identify praja2 as a novel upstream regulator of the Hippo cascade, linking the ubiquitin proteasome system to deregulated glioblastoma growth.

Original languageEnglish
Article number1822
JournalNature Communications
Publication statusPublished - 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)


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