Dissect The Hak Function In Hippo Pathway

How organs achieve an appropriate size during development is a fundamental important question.Many experiments have identified multiple regulators of organ size in the past few decades.The Hippo(Hpo)pathway is one of the major conserved mechanisms that control organ size in both fruit fly and mammals.Many components of the pathway are identified as tumor suppressors.Misregulation of Hippo signaling has been reported in congenital diseases and several kinds of human cancers.In Drosophila,the transduction of Hpo signaling is mainly composed of a series of phosphorylation cascades,ultimately through regulating the phosphorylation level of the transcription coactivator Yorkie(YKi)to control cell growth and organ size through maintaining the cell proliferation and apoptosis process.In a RNAi screen,we identified a novel regulator of Hippo signaling,Hak,which positively regulates Hippo signaling activity in Drosophila.Furthermore,we find that Hak functions as a kinase to regulate Hippo signaling in a kinase activity dependent manner.In addition,we show that Hak regulates Hippo signaling through Yki.We also provide biochemical evidence that Hak interacts Hpo and causes its gel-shift.Taken together,our preliminary study indicates that Hak may regulate Hpo pathway through modulating Hpo phosphorylation.