title: TGEV nucleocapsid protein induces cell cycle arrest and apoptosis through activation of p53 signaling.
abstract: Our previous studies showed that TGEV infection could induce cell cycle arrest and apoptosis via activation of p53 signaling in cultured host cells. However, it is unclear which viral gene causes these effects. In this study, we investigated the effects of TGEV nucleocapsid (N) protein on PK-15 cells. We found that TGEV N protein suppressed cell proliferation by causing cell cycle arrest at the S and G2/M phases and apoptosis. Characterization of various cellular proteins that are involved in regulating cell cycle progression demonstrated that the expression of N gene resulted in an accumulation of p53 and p21, which suppressed cyclin B1, cdc2 and cdk2 expression. Moreover, the expression of TGEV N gene promoted translocation of Bax to mitochondria, which in turn caused the release of cytochrome c, followed by activation of caspase-3, resulting in cell apoptosis in the transfected PK-15 cells following cell cycle arrest. Further studies showed that p53 inhibitor attenuated TGEV N protein induced cell cycle arrest at S and G2/M phases and apoptosis through reversing the expression changes of cdc2, cdk2 and cyclin B1 and the translocation changes of Bax and cytochrome c induced by TGEV N protein. Taken together, these results demonstrated that TGEV N protein might play an important role in TGEV infection-induced p53 activation and cell cycle arrest at the S and G2/M phases and apoptosis occurrence.
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, PR China; College of Life Sciences, Hainan Normal University, Haikou, Hainan 571158, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Du
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Dong
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, PR China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, PR China.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, PR China.
authors.forename: Xingang
authors.initials: X
authors.lastname: Xu
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, PR China. Electronic address: dwtong@nwsuaf.edu.cn.
authors.forename: Dewen
authors.initials: D
authors.lastname: Tong
mesh_terms: D000818:Animals; D017209:Apoptosis; D059447:Cell Cycle Checkpoints; D002460:Cell Line; D005761:Gastroenteritis, Transmissible, of Swine / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D015870:Gene Expression; D054884:Host-Pathogen Interactions; D019590:Nucleocapsid Proteins / Q000235:genetics / Q000378:metabolism*; D013552:Swine / Q000821:virology*; D005760:Transmissible gastroenteritis virus / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D019590:Nucleocapsid Proteins; D016159:Tumor Suppressor Protein p53
keywords: Apoptosis; Cell cycle arrest; N protein; TGEV; p53 signaling