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Cells 2019, 8(2), 98; https://doi.org/10.3390/cells8020098

Targeting Hedgehog Signalling through the Ubiquitylation Process: The Multiple Roles of the HECT-E3 Ligase Itch

1
Center for Life [email protected], Istituto Italiano di Tecnologia, 00161 Rome, Italy
2
Department of Molecular Medicine, University of Rome La Sapienza, 00161 Rome, Italy
3
Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome La Sapienza, 00161 Rome, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 28 December 2018 / Revised: 24 January 2019 / Accepted: 26 January 2019 / Published: 29 January 2019
(This article belongs to the Special Issue Targeting Hedgehog Signaling in Cancer)
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Abstract

Hedgehog signalling (Hh) is a developmental conserved pathway strongly involved in cancers when deregulated. This important pathway is orchestrated by numerous regulators, transduces through distinct routes and is finely tuned at multiple levels. In this regard, ubiquitylation processes stand as essential for controlling Hh pathway output. Although this post-translational modification governs proteins turnover, it is also implicated in non-proteolytic events, thereby regulating the most important cellular functions. The HECT E3 ligase Itch, well known to control immune response, is emerging to have a pivotal role in tumorigenesis. By illustrating Itch specificities on Hh signalling key components, here we review the role of this HECT E3 ubiquitin ligase in suppressing Hh-dependent tumours and explore its potential as promising target for innovative therapeutic approaches. View Full-Text
Keywords: Hedgehog; cancer; ubiquitylation; Itch; Numb; β-arrestin2; GLI1; SuFu; Patched1 Hedgehog; cancer; ubiquitylation; Itch; Numb; β-arrestin2; GLI1; SuFu; Patched1
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Infante, P.; Lospinoso Severini, L.; Bernardi, F.; Bufalieri, F.; Di Marcotullio, L. Targeting Hedgehog Signalling through the Ubiquitylation Process: The Multiple Roles of the HECT-E3 Ligase Itch. Cells 2019, 8, 98.

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