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
Affiliations
- Paola Infante
- Center for Life NanoScience@Sapienza, Istituto Italiano di Tecnologia
- Roberta Faedda
- Department of Molecular Medicine, University La Sapienza
- Flavia Bernardi
- Department of Molecular Medicine, University La Sapienza
- Francesca Bufalieri
- Department of Molecular Medicine, University La Sapienza
- Ludovica Lospinoso Severini
- Department of Molecular Medicine, University La Sapienza
- Romina Alfonsi
- Department of Molecular Medicine, University La Sapienza
- Daniela Mazzà
- Department of Molecular Medicine, University La Sapienza
- Mariangela Siler
- Department of Molecular Medicine, University La Sapienza
- Sonia Coni
- Department of Molecular Medicine, University La Sapienza
- Agnese Po
- Department of Molecular Medicine, University La Sapienza
- Marialaura Petroni
- Center for Life NanoScience@Sapienza, Istituto Italiano di Tecnologia
- Elisabetta Ferretti
- Department of Experimental Medicine, University La Sapienza
- Mattia Mori
- Center for Life NanoScience@Sapienza, Istituto Italiano di Tecnologia
- Enrico De Smaele
- Department of Experimental Medicine, University La Sapienza
- Gianluca Canettieri
- Department of Molecular Medicine, University La Sapienza
- Carlo Capalbo
- Department of Molecular Medicine, University La Sapienza
- Marella Maroder
- Department of Medico-Surgical Sciences and Biotechnologies, University La Sapienza
- Isabella Screpanti
- Department of Molecular Medicine, University La Sapienza
- Marcel Kool
- Hopp Children’s Cancer Center at the NCT (KiTZ)
- Stefan M. Pfister
- Hopp Children’s Cancer Center at the NCT (KiTZ)
- Daniele Guardavaccaro
- Hubrecht Institute-KNAW and University Medical Center Utrecht
- Alberto Gulino
- Department of Molecular Medicine, University La Sapienza
- Lucia Di Marcotullio
- Department of Molecular Medicine, University La Sapienza
- DOI
- https://doi.org/10.1038/s41467-018-03339-0
- Journal volume & issue
-
Vol. 9,
no. 1
pp. 1 – 17
Abstract
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.