Nature Communications (Mar 2018)

Itch/β-arrestin2-dependent non-proteolytic ubiquitylation of SuFu controls Hedgehog signalling and medulloblastoma tumorigenesis

  • Paola Infante,
  • Roberta Faedda,
  • Flavia Bernardi,
  • Francesca Bufalieri,
  • Ludovica Lospinoso Severini,
  • Romina Alfonsi,
  • Daniela Mazzà,
  • Mariangela Siler,
  • Sonia Coni,
  • Agnese Po,
  • Marialaura Petroni,
  • Elisabetta Ferretti,
  • Mattia Mori,
  • Enrico De Smaele,
  • Gianluca Canettieri,
  • Carlo Capalbo,
  • Marella Maroder,
  • Isabella Screpanti,
  • Marcel Kool,
  • Stefan M. Pfister,
  • Daniele Guardavaccaro,
  • Alberto Gulino,
  • Lucia Di Marcotullio

DOI
https://doi.org/10.1038/s41467-018-03339-0
Journal volume & issue
Vol. 9, no. 1
pp. 1 – 17

Abstract

Read online

SuFu is a tumour suppressor in medulloblastoma and regulates Gli proteins in the Sonic Hedgehog pathway; however, the molecular mechanisms behind this regulation are unclear. Here, the authors show that the Itch/β-arrestin2 complex binds and ubiquitylates SuFu, facilitating the interaction with Gli3 and its conversion into the repressive form, thus counteracting medulloblastoma formation.