PUBLICATION
Deubiquitination of Ci/Gli by Usp7/HAUSP Regulates Hedgehog Signaling
- Authors
- Zhou, Z., Yao, X., Li, S., Xiong, Y., Dong, X., Zhao, Y., Jiang, J., Zhang, Q.
- ID
- ZDB-PUB-240502-28
- Date
- 2015
- Source
- Developmental Cell 34: 587258-72 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- DNA-Binding Proteins/metabolism*
- Drosophila Proteins/metabolism*
- Drosophila melanogaster/metabolism*
- Hedgehog Proteins/metabolism*
- Protein Processing, Post-Translational/physiology
- Signal Transduction*
- Transcription Factors/metabolism*
- Ubiquitin/metabolism
- Ubiquitination/physiology*
- PubMed
- 26120032 Full text @ Dev. Cell
Citation
Zhou, Z., Yao, X., Li, S., Xiong, Y., Dong, X., Zhao, Y., Jiang, J., Zhang, Q. (2015) Deubiquitination of Ci/Gli by Usp7/HAUSP Regulates Hedgehog Signaling. Developmental Cell. 34:587258-72.
Abstract
Hedgehog (Hh) signaling plays essential roles in animal development and tissue homeostasis, and its misregulation causes congenital diseases and cancers. Regulation of the ubiquitin/proteasome-mediated proteolysis of Ci/Gli transcription factors is central to Hh signaling, but whether deubiquitinase is involved in this process remains unknown. Here, we show that Hh stimulates the binding of a ubiquitin-specific protease Usp7 to Ci, which positively regulates Hh signaling activity through inhibiting Ci ubiquitination and degradation mediated by both Slimb-Cul1 and Hib-Cul3 E3 ligases. Furthermore, we find that Usp7 forms a complex with GMP-synthetase (GMPS) to promote Hh pathway activity. Finally, we show that the mammalian counterpart of Usp7, HAUSP, positively regulates Hh signaling by modulating Gli ubiquitination and stability. Our findings reveal a conserved mechanism by which Ci/Gli is stabilized by a deubiquitination enzyme and identify Usp7/HUASP as a critical regulator of Hh signaling and potential therapeutic target for Hh-related cancers.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping