title: Enterovirus 71 3C Promotes Apoptosis through Cleavage of PinX1, a Telomere Binding Protein.
abstract: Enterovirus 71 (EV71) is an emerging pathogen causing hand, foot, and mouth disease (HFMD) and fatal neurological diseases in infants and young children due to their underdeveloped immunocompetence. EV71 infection can induce cellular apoptosis through a variety of pathways, which promotes EV71 release. The viral protease 3C plays an important role in EV71-induced apoptosis. However, the molecular mechanism responsible for 3C-triggered apoptosis remains elusive. Here, we found that EV71 3C directly interacted with PinX1, a telomere binding protein. Furthermore, 3C cleaved PinX1 at the site of Q50-G51 pair through its protease activity. Overexpression of PinX1 reduced the level of EV71-induced apoptosis and EV71 release, whereas depletion of PinX1 by small interfering RNA promoted apoptosis induced by etoposide and increased EV71 release. Taken together, our study uncovered a mechanism that EV71 utilizes to promote host cell apoptosis through cleavage of cellular protein PinX1 by 3C.
  
  
  OBJECTIVE
  EV71 3C plays an important role in processing viral proteins and interacting with host cells. In this study, we showed that 3C promoted apoptosis through cleaving PinX1, a telomere binding protein, and that this cleavage facilitated EV71 release. Our study demonstrated that PinX1 plays an important role in EV71 release and revealed a novel mechanism that EV71 utilizes to induce apoptosis. This finding is important in understanding EV71-host cell interactions and has potential impact on understanding other enterovirus-host cell interactions.
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Yunfang
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Xu
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Division of Biology, Kansas State University, Manhattan, Kansas, USA.
authors.forename: Zhilong
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China wentaoqiao@nankai.edu.cn juantan@nankai.edu.cn.
authors.forename: Wentao
authors.initials: W
authors.lastname: Qiao
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China wentaoqiao@nankai.edu.cn juantan@nankai.edu.cn.
authors.forename: Juan
authors.initials: J
authors.lastname: Tan
mesh_terms: D000086042:3C Viral Proteases; D017209:Apoptosis / Q000187:drug effects; D018797:Cell Cycle Proteins; D002460:Cell Line; D003384:Coxsackievirus Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D029821:Enterovirus A, Human / Q000502:physiology*; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D011485:Protein Binding; D059748:Proteolysis; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*; D057074:Virus Release
chemical_list: D018797:Cell Cycle Proteins; C440808:PINX1 protein, human; D034501:Telomere-Binding Proteins; D025521:Tumor Suppressor Proteins; D014764:Viral Proteins; D005047:Etoposide; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases
keywords: 3C; PinX1; apoptosis; enterovirus 71