title: Proteolysis of MOB1 by the ubiquitin ligase praja2 attenuates Hippo signalling and supports glioblastoma growth.
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.
authors: Dipartimento di Medicina Molecolare and Biotecnologie Mediche, University Federico II and IEOS-CNR, 80131 Naples, Italy.
authors: Luca
authors: L
authors: Lignitto
authors: Antonietta
authors: A
authors: Arcella
authors: Maria
authors: M
authors: Sepe
authors: Laura
authors: L
authors: Rinaldi
authors: Rossella
authors: R
authors: Delle Donne
authors: Adriana
authors: A
authors: Gallo
authors: Eduard
authors: E
authors: Stefan
authors: Verena A
authors: VA
authors: Bachmann
authors: Maria A
authors: MA
authors: Oliva
authors: Clelia
authors: C
authors: Tiziana Storlazzi
authors: Alberto
authors: A
authors: L'Abbate
authors: Arturo
authors: A
authors: Brunetti
authors: Sara
authors: S
authors: Gargiulo
authors: Matteo
authors: M
authors: Gramanzini
authors: Luigi
authors: L
authors: Insabato
authors: Corrado
authors: C
authors: Garbi
authors: Max E
authors: ME
authors: Gottesman
authors: Antonio
authors: A
authors: Feliciello
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001932:Brain Neoplasms / Q000201:enzymology / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005909:Glioblastoma / Q000201:enzymology / Q000473:pathology*; D057809:HEK293 Cells; D000090683:Hippo Signaling Pathway; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D008969:Molecular Sequence Data; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D059748:Proteolysis; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C496256:MOB1A protein, human; C577689:PJA2 protein, human; D044767:Ubiquitin-Protein Ligases; D017346:Protein Serine-Threonine Kinases
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