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

Author

Listed:
  • Luca Lignitto

    (University Federico II and IEOS-CNR)

  • Antonietta Arcella

    (I.R.C.C.S Neuromed Località Camerelle)

  • Maria Sepe

    (University Federico II and IEOS-CNR)

  • Laura Rinaldi

    (University Federico II and IEOS-CNR)

  • Rossella Delle Donne

    (University Federico II and IEOS-CNR)

  • Adriana Gallo

    (University Federico II and IEOS-CNR)

  • Eduard Stefan

    (Institute of Biochemistry and Center for Molecular Biosciences Innsbruck (CMBI), Innrain 80/82)

  • Verena A. Bachmann

    (Institute of Biochemistry and Center for Molecular Biosciences Innsbruck (CMBI), Innrain 80/82)

  • Maria A. Oliva

    (I.R.C.C.S Neuromed Località Camerelle)

  • Clelia Tiziana Storlazzi

    (University of Bari)

  • Alberto L'Abbate

    (University of Bari)

  • Arturo Brunetti

    (CEINGE Biotecnologie Avanzate Scarl, University Federico II)

  • Sara Gargiulo

    (CEINGE Biotecnologie Avanzate Scarl, University Federico II)

  • Matteo Gramanzini

    (CEINGE Biotecnologie Avanzate Scarl, University Federico II)

  • Luigi Insabato

    (CEINGE Biotecnologie Avanzate Scarl, University Federico II)

  • Corrado Garbi

    (University Federico II and IEOS-CNR)

  • Max E. Gottesman

    (Institute of Cancer Research, Columbia University Medical Center)

  • Antonio Feliciello

    (University Federico II and IEOS-CNR)

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.

Suggested Citation

  • 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'Abba, 2013. "Proteolysis of MOB1 by the ubiquitin ligase praja2 attenuates Hippo signalling and supports glioblastoma growth," Nature Communications, Nature, vol. 4(1), pages 1-13, June.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2791
    DOI: 10.1038/ncomms2791
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    Cited by:

    1. Samira Schiefer & Benjamin G. Hale, 2024. "Proximal protein landscapes of the type I interferon signaling cascade reveal negative regulation by PJA2," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Mengjia Lin & Xiaoyun Zheng & Jianing Yan & Fei Huang & Yilin Chen & Ran Ding & Jinkai Wan & Lei Zhang & Chenliang Wang & Jinchang Pan & Xiaolei Cao & Kaiyi Fu & Yan Lou & Xin-Hua Feng & Junfang Ji & , 2024. "The RNF214-TEAD-YAP signaling axis promotes hepatocellular carcinoma progression via TEAD ubiquitylation," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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