Vlet,a COMMD Family Protein,Associates with Wts to Suppress Hippo Signaling in Drosophila
The Hippo signaling pathway plays an important role in controlling organ size and tumorigenesis by regulating cell proliferation and apoptosis and maintaining cell homeostasis.Wts is a core component of the Hippo signaling pathway and its activity needs to be controlled strictly.Therefore,many attentions are attracting to identify new regulators of Wts.In this study,Vlet,a COMMD protein family member,is identified as a new Wts regulator in Drosophila through immunoprecipitation and mass spectrometry analysis(IP-MS).Vlet associates with the catalytic domain of Wts and decrease Wts activity by inhibiting Wts-T1077 phosphorylation in Drosophila S2 cells.Consistently,in vivo genetics analysis in Drosophila animal found that the small wing phenotype caused by Wts overexpression is significantly rescued by Vlet overexpression.Taken together,our studies demonstrate Vlet is a novel modulator of Wts activity and may have implications in human diseases related to dysregulation of COMMD family on Hippo signaling.
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