Proteolysis of MOB1 by the Ubiquitin Ligase Praja2 Attenuates Hippo Signalling and Supports Glioblastoma Growth

Overview

Journal Nat Commun

Specialty Biology

Date 2013 May 9

PMID 23652010

Citations 65

Authors

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 LAbbate

Arturo Brunetti

Sara Gargiulo

Matteo Gramanzini

Luigi Insabato

Corrado Garbi

Max E Gottesman

Antonio Feliciello

Affiliations

Soon will be listed here.

Abstract

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.

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