NDLI: A Targeted In Vivo RNAi Screen Reveals Deubiquitinases as New Regulators of Notch Signaling

Content Provider	PubMed Central
Author	Zhang, Junzheng Liu, Min Su, Ying Du, Juan Zhu, Alan Jian
Copyright Year	2012
Abstract	Notch signaling is highly conserved in all metazoan animals and plays critical roles in cell fate specification, cell proliferation, apoptosis, and stem cell maintenance. Although core components of the Notch signaling cascade have been identified, many gaps in the understanding of the Notch signaling pathway remain to be filled. One form of posttranslational regulation, which is controlled by the ubiquitin-proteasome system, is known to modulate Notch signaling. The ubiquitination pathway is a highly coordinated process in which the ubiquitin moiety is either conjugated to or removed from target proteins by opposing E3 ubiquitin ligases and deubiquitinases (DUBs). Several E3 ubiquitin ligases have been implicated in ubiquitin conjugation to the receptors and the ligands of the Notch signaling cascade. In contrast, little is known about a direct role of DUBs in Notch signaling in vivo. Here, we report an in vivo RNA interference screen in Drosophila melanogaster targeting all 45 DUBs that we annotated in the fly genome. We show that at least four DUBs function specifically in the formation of the fly wing margin and/or the specification of the scutellar sensory organ precursors, two processes that are strictly dependent on the balanced Notch signaling activity. Furthermore, we provide genetic evidence suggesting that these DUBs are necessary to positively modulate Notch signaling activity. Our study reveals a conserved molecular mechanism by which protein deubiquitination process contributes to the complex posttranslational regulation of Notch signaling in vivo.
Related Links	http://dx.doi.org/10.1534/g3.112.003780
Ending Page	1575
Page Count	13
Starting Page	1563
File Format	PDF
ISSN	21601836
e-ISSN	21601836
Journal	G3: Genes\|Genomes\|Genetics
Issue Number	12
Volume Number	2
Language	English
Publisher	Genetics Society of America
Publisher Date	2012-12-01
Access Restriction	Open
Rights Holder	Genetics Society of America
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics Molecular Biology Genetics (clinical)

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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