Researchers Discover a Novel Regulator of Canonical Wnt Signaling Pathway
Source:
Time: 2012-08-04
Wnt signaling pathway regulates multiple developmental events during embryogenesis and has also been implicated in tumorigenesis. Recently, Dr. LI Lin’s group at Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, identified a new regulator of canonical Wnt signaling pathway, an E3 ubiquitin ligase specifically targeting the phosphorylated Dvl protein.
Dishevelled (Dvl) is a central mediator of Wnt signaling in both canonical and noncanonical pathways. In canonical Wnt pathway, Dvl plays dual roles in cytosol and nucleus respectively. Although it has been reported that the phosphorylation of Dvl is required for canonical Wnt signaling transduction, the regulation of the Dvl activity is incompletely understood. In this work, WEI wei and colleagues from LI Lin’s group disclosed that E3 ubiquitin ligase ITCH promotes the ubiquitination and proteosome-dependent degradation of phosphorylated Dvl. The finding is intriguing for ITCH only targets the phosphorylated form of Dvl, which is different from other already found E3 ubiquitin ligases for Dvl. In addition, their results also show that, via regulating the stability of phosphorylated Dvl, ITCH plays a negative role in canonical Wnt signaling.
This study further improves our knowledge about Wnt signaling transduction network, and reveals a novel molecular mechanism on modulation of the activity and stability of Dvl in canonical Wnt signaling. On the other side, this work functionally connects ITCH with canonical Wnt signaling, which plays pivotal roles in many kinds of cancers, may provide new clues for further studies in direct correlation of ITCH with cancer biology.
This work entitled “The E3 Ubiquitin Ligase ITCH Negatively Regulates Canonical Wnt Signaling by Targeting Dishevelled Protein” has been published online in Molecular and Cellular Biology on July 23rd, 2012, before its appearance in print.
This work is supported by grants from the Ministry of Science and Technology of China, and the National Natural Science Foundation of China.
AUTHOR CONTACT:
LI Lin
Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China
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