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
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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COS Cells
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Cell Proliferation*
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Chlorocebus aethiops
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Data Interpretation, Statistical
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Gene Expression Regulation, Neoplastic
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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HeLa Cells
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Humans
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Intercellular Signaling Peptides and Proteins / genetics
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Intercellular Signaling Peptides and Proteins / metabolism
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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Proto-Oncogene Mas
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism*
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Securin
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beta-Transducin Repeat-Containing Proteins / genetics
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beta-Transducin Repeat-Containing Proteins / metabolism*
Substances
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BTRC protein, human
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Intercellular Signaling Peptides and Proteins
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Intracellular Signaling Peptides and Proteins
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MAS1 protein, human
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Membrane Proteins
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Neoplasm Proteins
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PTTG1IP protein, human
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Proto-Oncogene Mas
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Recombinant Fusion Proteins
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Securin
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beta-Transducin Repeat-Containing Proteins
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enhanced green fluorescent protein
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pituitary tumor-transforming protein 1, human
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Green Fluorescent Proteins