TIP-1 is a Degradation Target of HPV-16 E6

Document Type : Original Article

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1 medical biochemistry and molecular biology, faculty of medicine , mansoura university,mansoura egypt

2 Tumor Virology Group, I.C.G.E.B., AREA Science Park, Padriciano 99, Trieste, Italy

Abstract

Background: The high risk Human Papilloma virus E6 oncoprotein plays an essential role in the development and maintenance of malignancy through its ability to target several PDZ domain containing proteins one of them is a small PDZ protein called Tax-interacting protein 1 (TIP-1). Tip-1 is known to affect the cancer pathway through regulation of Rho and wnt/β-catenin signaling pathways. It also regulates many cellular processes through its interaction with several cellular proteins, including the tax protein, LIN7,MAGI‐1, PlexinD1 , AHDC1, L-glutaminase and Kir2.3. Methods: GST pull down assays , In vitro degradation assays, cell culture and co-transfectio, Immunofluorescent assays and western blot were used to analyse cellular expression levels of TIP-1. Result: TIP-1 was shown to be degraded when co-transfected with E6s from three different cancer-causing HPV types (HPV-16, HPV-18, and HPV-33E6) co-transfection was repeated in the presence of CBZ and we shown by western blot the appearance of Tip-1 again . Also , the co-transfection was repeated in the absence of E6AP and was shown by western blot the appearance of Tip-1 again. Immunofluorescent assay have shown an increase of Tip-1expression in presence of CBZ. Conclusion: Tip-1 is degraded by three different cancer-causing HPV types (HPV-16, HPV-18, and HPV-33E6) This degradation also appears to be dependent on the presence of the E6-AP (UBE3A) protein-ubiquitin ligase. This suggests that TIP-1 is a common target of high-risk HPV types.

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