Hedgehog/Gli Control by Ubiquitination/Acetylation Interplay

Alberto Gulino, Lucia Di Marcotullio, Gianluca Canettieri, Enrico De Smaele, Isabella Screpanti

Research output: Contribution to journalArticle

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 E3 ligases belonging to the RING/Cullin and HECT families. These E3 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 HDAC1-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.

Original languageEnglish
Pages (from-to)211-227
Number of pages17
JournalVitamins and Hormones
Volume88
DOIs
Publication statusPublished - 2012

Keywords

  • Gli
  • HECT E3 ligases
  • Hedgehog
  • Histone deacetylases
  • RING E3 ligases
  • Ubiquitin

ASJC Scopus subject areas

  • Endocrinology
  • Physiology

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    Gulino, A., Di Marcotullio, L., Canettieri, G., De Smaele, E., & Screpanti, I. (2012). Hedgehog/Gli Control by Ubiquitination/Acetylation Interplay. Vitamins and Hormones, 88, 211-227. https://doi.org/10.1016/B978-0-12-394622-5.00009-2