Hedgehog is a key morphogen regulating development and leading to tumorigenesis, when hyperactivated. Hedgehog signaling is mediated by transcriptional effectors belonging to the Gli family. Ubiquitination-related posttranslational modifications of the Gli transcription factors, leading to proteasome-dependent proteolytic cleavage or massive degradation, represent an important mechanism of regulation of the pathway. Gli ubiquitination is controlled by a number of E-3 ligases belonging to the RING/Cullin and HECT families. These E-3 ligases are regulated by several members of the Hh pathway itself (e.g., Smo-activated kinases) as well as by proteins belonging to other signaling cascades (i.e., Numb-activated Itch). These proteolytic signals finally suppress Gli function either directly or indirectly (i.e., suppression of HDAC(1)-mediated Gli deacetylation). The complex of these regulatory circuitries finely tunes Hedgehog signaling providing a tight control of developmental processes, the subversion of which leads to tumorigenesis. To this regard, these ubiquitination processes represent promising targets for novel therapeutic strategies. (C) 2012 Elsevier Inc.

Hedgehog/Gli Control by Ubiquitination/Acetylation Interplay / Gulino, Alberto; DI MARCOTULLIO, Lucia; Canettieri, Gianluca; DE SMAELE, Enrico; Screpanti, Isabella. - STAMPA. - 88(2012), pp. 211-227. [10.1016/b978-0-12-394622-5.00009-2].

Hedgehog/Gli Control by Ubiquitination/Acetylation Interplay

GULINO, Alberto;DI MARCOTULLIO, LUCIA;CANETTIERI, Gianluca;DE SMAELE, Enrico;SCREPANTI, Isabella
2012

Abstract

Hedgehog is a key morphogen regulating development and leading to tumorigenesis, when hyperactivated. Hedgehog signaling is mediated by transcriptional effectors belonging to the Gli family. Ubiquitination-related posttranslational modifications of the Gli transcription factors, leading to proteasome-dependent proteolytic cleavage or massive degradation, represent an important mechanism of regulation of the pathway. Gli ubiquitination is controlled by a number of E-3 ligases belonging to the RING/Cullin and HECT families. These E-3 ligases are regulated by several members of the Hh pathway itself (e.g., Smo-activated kinases) as well as by proteins belonging to other signaling cascades (i.e., Numb-activated Itch). These proteolytic signals finally suppress Gli function either directly or indirectly (i.e., suppression of HDAC(1)-mediated Gli deacetylation). The complex of these regulatory circuitries finely tunes Hedgehog signaling providing a tight control of developmental processes, the subversion of which leads to tumorigenesis. To this regard, these ubiquitination processes represent promising targets for novel therapeutic strategies. (C) 2012 Elsevier Inc.
2012
Hedgehog Signaling
9780123946225
hect e3 ligases; hedgehog; ring e3 ligases; histone deacetylases; ubiquitin; gli
02 Pubblicazione su volume::02a Capitolo o Articolo
Hedgehog/Gli Control by Ubiquitination/Acetylation Interplay / Gulino, Alberto; DI MARCOTULLIO, Lucia; Canettieri, Gianluca; DE SMAELE, Enrico; Screpanti, Isabella. - STAMPA. - 88(2012), pp. 211-227. [10.1016/b978-0-12-394622-5.00009-2].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/444530
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