Antitumor effect of F-PBF beta-TrCP-induced targeted PTTG1 degradation in HeLa cells

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. (c) 2008 Elsevier B.V. All rights reserved.