title: Antitumor effect of F-PBF(beta-TrCP)-induced targeted PTTG1 degradation in HeLa cells.
abstract: Pituitary tumor-transforming gene 1 (PTTG1), a proto-oncogene, is associated with tumor formation, proliferation and invasiveness. F-PBF(beta-TrCP), a fusion protein, was produced by replacing the WD40-repeat of F-box protein beta-TrCP with the PTTG1-binding factor (PBF) for targeted degradation of PTTG1. To evaluate the function of F-PBF(beta-TrCP), PTTG1-EGFP fusion protein was constructed. Our results showed that F-PBF(beta-TrCP) can both degrade exogenous PTTG1-EGFP fusion protein in COS-7 cells and endogenous PTTG1 protein in HeLa cells and the targeted PTTG1 knock down resulted in bFGF mRNA level down-regulation and inhibition of proliferation and clonogenicity in HeLa cells. In conclusion, targeted degradation of PTTG1 by F-PBF(beta-TrCP) has antitumor activity in vitro in HeLa cells. These results suggest that F-PBF(beta-TrCP) could be used for cancer treatment by targeted degradation of PTTG1.
authors.affiliation: The Key Laboratory of Chemical Biology, Guangdong Province, Graduate School at Shenzhen, Tsinghua University, Shenzhen, Guangdong 518055, People's Republic of China.
authors.forename: Zhuohua
authors.initials: Z
authors.lastname: Mo
authors.forename: Xuyu
authors.initials: X
authors.lastname: Zu
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Xie
authors.forename: Wenpeng
authors.initials: W
authors.lastname: Li
authors.forename: Hang
authors.initials: H
authors.lastname: Ning
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Jiang
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
mesh_terms: D000818:Animals; D019556:COS Cells; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D003627:Data Interpretation, Statistical; D015972:Gene Expression Regulation, Neoplastic; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D064249:Securin; D044844:beta-Transducin Repeat-Containing Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C471644:BTRC protein, human; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; C000715470:MAS1 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C112633:PTTG1IP protein, human; D000090063:Proto-Oncogene Mas; D011993:Recombinant Fusion Proteins; D064249:Securin; D044844:beta-Transducin Repeat-Containing Proteins; C485184:enhanced green fluorescent protein; C578002:pituitary tumor-transforming protein 1, human; D049452:Green Fluorescent Proteins