肌营养不良蛋白dys参与调控Hippo信号通路  

Muscular Dystrophy Protein Dys Is Involved in Regulating Hippo Signaling Pathway

作　　者：张晓亭 吴世安[1] Zhang Xiaoting;Wu Shian(College of Life Sciences,Nankai University,Tianjin 300071,China)

机构地区：[1]南开大学生命科学学院,天津300071

出　　处：《南开大学学报（自然科学版）》2021年第3期41-47,共7页Acta Scientiarum Naturalium Universitatis Nankaiensis

基　　金：国家自然科学基金(31871992,31371974);药物化学生物学国家重点实验室开放基金。

摘　　要：Hippo信号通路最早在黑腹果蝇中发现,现已被证明在哺乳动物中也是保守的.Hippo通路在器官发育和组织稳态中起着重要作用,Hippo信号通路异常与许多癌症的发生相关.Hippo信号通路依赖于核心激酶级联反应,磷酸化转录共激活因子Yorkie(Yki)进而调控下游靶基因的转录.尽管Wts是Hippo通路的关键激酶组分,但其蛋白质活性调节机制仍有待深入研究.通过质谱分析,发现并验证了Hippo信号通路核心激酶Wts与杜氏肌营养不良症相关蛋白dys之间存在相互作用,并发现dys能够通过促进Wts的细胞膜定位激活Wts进而调控果蝇器官大小.The Hippo signaling pathway was first discovered in drosophila melanogaster and has been proved to be conserved in mammals.The Hippo pathway plays an important role in organ development and tissue homeostasis,and dysregulation of Hippo signaling is related to the occurrence of many cancers.The Hippo pathway is featured by a core kinase cascade composed of upstream kinase Hippo(Hpo)and downstream kinase Warts(Wts),and the coactivator Yorkie(Yki)phosphorylated by activated Wts to regulate the transcription of target genes in a Scalloped(Sd)-dependent manner.Although Wts is a key component in Hippo signaling,the regulatory mechanism of its activity is still incompletely.Using immunoprecipitation and mass spectrometry analysis,we found and verified the interaction between Wts and dys,a protein related to Duchenne muscular dystrophy.Further studies uncovered that Wts was trans-localized to cytoplasm membrane and probably activated by dys in drosophila,suggesting a novel molecular mechanism of dys in organ size control through the Hippo tumor suppression pathway.

关 键 词：Hippo信号通路 Wts dys 器官大小 

分 类 号：Q78[生物学—分子生物学]