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The PTPN14 Tumor Suppressor Is a Degradation Target of Human Papillomavirus E7

Szalmás, Anita; Tomaić, Vjekoslav; Basukala, Om; Massimi, Paola; Mittal, Suruchi; Kónya, József; Banks, Lawrence (2017) The PTPN14 Tumor Suppressor Is a Degradation Target of Human Papillomavirus E7. Journal of Virology, 91 (7). ISSN 0022-538X

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Activation of signaling pathways ensuring cell growth is essential for the proliferative competence of human papillomavirus (HPV)-infected cells. Tyrosine kinases and phosphatases are key regulators of cellular growth control pathways. A recently identified potential cellular target of HPV E7 is the cytoplasmic protein tyrosine phosphatase PTPN14, which is a potential tumor suppressor and is linked to the control of the Hippo and Wnt/beta-catenin signaling pathways. In this study, we show that the E7 proteins of both high-risk and low-risk mucosal HPV types can interact with PTPN14. This interaction is independent of retinoblastoma protein (pRb) and involves residues in the carboxy-terminal region of E7. We also show that high-risk E7 induces proteasome-mediated degradation of PTPN14 in cells derived from cervical tumors. This degradation appears to be independent of cullin-1 or cullin-2 but most likely involves the UBR4/p600 ubiquitin ligase. The degree to which E7 downregulates PTPN14 would suggest that this interaction is important for the viral life cycle and potentially also for the development of malignancy. In support of this we find that overexpression of PTPN14 decreases the ability of HPV-16 E7 to cooperate with activated EJ-ras in primary cell transformation assays.

Item Type: Article
Additional Information: This work was supported partly by the Campus Hungary Fellowship for Higher Education Staff Mobility (B2/4R/19122 and B2/4H/13274), an ICGEB Arturo Falachi Postdoctoral Fellowship awarded to A.S., and a research grant from the Associazione Italiana per la Ricerca sul Cancro awarded to L.B.
Uncontrolled Keywords: human papillomavirus; E7; PTPN14; transformation; tyrosine phosphatases
Divisions: Division of Molecular Medicine
Depositing User: Vjekoslav Tomaić
Date Deposited: 13 Nov 2018 14:35
DOI: 10.1128/JVI.00057-17

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