A team of scientists led by ZHANG Lei at Institute of Biochemistry and Cell Biology, Shanghai Institutes of Biological Sciences, CAS, have uncovered a dual role of Casein Kinase 2 for growth control.
Casein Kinase 2 (CK2) is a tetrameric serine/theronine protein kinase. It is a key suppressor of apoptosis and is essential for cell survival, and is previously reported to phosphorylate components in a variety of signalling pathways. Yet, it remains unclear whether CK2 is involved in Hippo signalling.
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. The Hippo pathway functions through the inhibition of the transcriptional coactivator Yorkie by a series of phosphorylation events. Hippo and Warts are the key kinases that induce these phosphorylation events. Upon Warts-induced phosphorylation, Yorkie fails to translocate into the nucleus to bind with transcription factors to induce the expression of genes promoting proliferation and inhibiting apoptosis. Enormous amounts of researches have focused on the study the inappropriate Yorkie activity induced overgrowth, which is believed to be related to human cancers.
To help elucidate the roles of CK2 in growth control, the scientists performed a series biochemical experiments to demonstrate that CK2 suppresses Yorkie activity via promoting Warts activity. Using Drosophila as model system, they demonstrated that this function of CK2 leads to growth inhibition. By loss-of-function analysis, they were able to show that loss of CK2 decreases Warts activity and upregulates Yorkie targets expression. However, they also showed that CK2 is necessary for tissue growth since loss of CK2 induces severe cell death and suppresses tissue growth. They proposed that the function of CK2 in promoting Warts activity is coordinated with its anti-apoptotic function, which fine-tunes cell proliferation and cell death.
“With this new understanding of how CK2’s function in growth control, our knowledge on growth control and cell survival is expanded.” said lead author ZHANG Lei. “However, lots of questions need to be answered in the further. What is the trigger to switch the dual role of CK2? How CK2 balance its roles to ensure a normal cell growth? Deep understanding of the underlying mechanism may help us to answer these questions.”
Their findings “Drosophila CK2 promotes Wts to suppress Yki activity for growth control”are published online in the Journal of Biological Chemistry on Oct 18, 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.
A-B: knockdown of CK2 suppresses tissue growth;
C-D’: knockdown of CK2 upregulates expression level of Yki target diap1-GFP
(Image provided by Prof. ZHANG Lei)
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