A team of scientists led by ZHANG Lei at the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences, have demonstrated the degradation mechanism of Hippo signaling upstream component Pez.
The highly conserved Hippo signaling pathway governs tissue growth and organ size by coordinating cell proliferation and apoptosis. As a tumor suppressor pathway, deregulation of Hippo signaling is closely related to tumorigenesis. Pez, as an upstream component of Hippo signaling, is required for the function of Hippo signaling. The loss of Pez activity induces overgrowth of Drosophila intestinal stem cells.
But how Pez affects Hippo signaling? WANG Chao, ZHANG Wenxiang and other members from Dr. ZHANG Lei`s group performed a series biochemical experiments and identified that Suppressor of Deltex (Su(dx)), an E3 ligase, mediates Pez degradation. Using Drosophila as model system, they demonstrated that Su(dx) promotes the degradation of Pez protein, leading to an overgrowth of Drosophila midguts. By molecular and biochemical analysis, they were able to show that Su(dx) and Pez intact through WW domains and PY/PPPY motifs. Meanwhile, they also showed that Kibra, an upstream Hippo signaling component, inhibits Su(dx)-induced Pez degradation.
“These findings improved our insight of the regulatory mechanism of the Hippo signaling pathway,” said Dr. Zhang, “we hope this work could shed some lights on identifying potential targets for therapeutic intervention and treatment of related cancers.”
This work entitled “Suppressor of Deltex mediates Pez degradation and modulates Drosophila midgut homeostasis” was published online by Nature Communications on March 27, 2015.
This work was supported by grants from Chinese Academy of Sciences, the Ministry of Science and Technology of China, and the National Natural Science Foundation of China.
Fig. A model of the regulation of Pez protein stability by Su(dx) and Kibra. Su(dx) ubiquitylates and degrades Pez and this process is inhibited by Kibra. (Image provided by Dr. ZHANG Lei’s group)
CONTACT:
ZHANG Lei, Principal Investigator
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
Shanghai 200031, China.
Email: rayzhang@sibcb.ac.cn
Phone: +86-21-54921336.
Appendix：
