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

J Biotechnol. 2009 Jan 1;139(1):6-11. doi: 10.1016/j.jbiotec.2008.09.004. Epub 2008 Oct 1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Cell Proliferation*
  • Chlorocebus aethiops
  • Data Interpretation, Statistical
  • Gene Expression Regulation, Neoplastic
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • HeLa Cells
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism*
  • Securin
  • beta-Transducin Repeat-Containing Proteins / genetics
  • beta-Transducin Repeat-Containing Proteins / metabolism*

Substances

  • BTRC protein, human
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Neoplasm Proteins
  • PTTG1IP protein, human
  • Recombinant Fusion Proteins
  • Securin
  • beta-Transducin Repeat-Containing Proteins
  • enhanced green fluorescent protein
  • pituitary tumor-transforming protein 1, human
  • Green Fluorescent Proteins