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001-es BibID:	BIBFORM070524
Első szerző:	Szalmás Anita (biológus, mikrobiológus, klinikai mikrobiológus)
Cím:	The PTPN14 tumour suppressor is a degradation target of Human Papillomavirus E7 / Anita Szalmás, Vjekoslav Tomaić, Om Basukala, Paola Massimi, Suruchi Mittal, József Kónya, Lawrence Banks
Dátum:	2017
ISSN:	0022-538X
Megjegyzések:	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.IMPORTANCE This study links HPV E7 to the deregulation of protein tyrosine phosphatase signaling pathways. PTPN14 is classified as a potential tumor suppressor protein, and here we show that it is very susceptible to HPV E7-induced proteasome-mediated degradation. Intriguingly, this appears to use a mechanism that is different from that employed by E7 to target pRb. Therefore, this study has important implications for our understanding of the molecular basis for E7 function and also sheds important light on the potential role of PTPN14 as a tumor suppressor.
Tárgyszavak:	Orvostudományok Egészségtudományok idegen nyelvű folyóiratközlemény külföldi lapban human papillomavirus transformation tyrosine phosphatases
Megjelenés:	Journal Of Virology 91 : 7 (2017), p. 1-13. -
További szerzők:	Tomaić, Vjekoslav Basukala, Om Massimi, Paola Mittal, Suruchi Kónya József (1964-) (szakorvos, klinikai mikrobiológus) Banks, Lawrence
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