title: TSP50 depends on its threonine protease activity and its interactions with TNF-α-induced NF-κB for its role in human cervical tumorigenesis.
abstract: Testes-specific protease 50 (TSP50) has threonine activity and has homology to serine proteases. TSP50 protein, which is encoded by a possible proto-oncogene, is overexpressed in cervical tumor tissues. Through overexpression experiments using both TSP50 and a TSP50 mutant (TSP50 T310A), it is clear that this protein may play an important role in carcinogenesis and progression of cervical tumor. However, the mechanism underlying how TSP50 modulates cancer cell growth is still unclear. To examine the difference in TSP50 expression in cervical carcinoma tissues and in paracarcinoma tissues, we detected TSP50 mRNA and protein in ten paired tissues from patients with cervical cancer. To determine whether TSP50's threonine protease activity is crucial for its effects on tumor formation, we generated a mutant version of TSP50 (T310A). Via overexpression and silencing experiments, we identified a role for TSP50 in cell proliferation and migration. Furthermore, we examined the signaling pathway of TNF-α-induced NFκB activation to explain the mechanism by which TSP50 participates in tumorigenesis. Similarly, we found that all these effects could be abolished by the TSP50 T310A mutation. Our results suggest that the threonine 310 residue within TSP50 helps modulate its role in cervical tumorigenesis and indicates that TSP50's role in tumorigenesis may be dependent on its interaction with TNF-α-induced NF-κB.
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Harbin Medical University, No. 23 Post Street, Nangang District, Harbin, 150001, Heilongjiang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.forename: ChunFeng
authors.initials: C
authors.lastname: Wu
authors.forename: MingLi
authors.initials: M
authors.lastname: Huang
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.forename: Wei
authors.initials: W
authors.lastname: Ben
authors.forename: GuangMei
authors.initials: G
authors.lastname: Zhang
mesh_terms: D063646:Carcinogenesis / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D012697:Serine Endopeptidases / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*
chemical_list: C000715470:MAS1 protein, human; D016328:NF-kappa B; D000090063:Proto-Oncogene Mas; D014409:Tumor Necrosis Factor-alpha; D012697:Serine Endopeptidases; C446379:testis-specific protease 50