Naslov
The PTPN14 tumour suppressor is a degradation target of Human Papillomavirus E7

Autori
Szalmás, Anita ; Tomaić, Vjekoslav ; Basukala, Om ; Massimi, Paola ; Mittal, Suruchi ; Kónya , József ; Banks, Lawrence

Izvornik
Journal of virology (0022-538X) 91 (2017), 7; E00057-17

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
human papillomavirus, E7, PTPN14, transformation, tyrosine phosphatases

Sažetak
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

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

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