Activation of cap-dependent translation by mucosal human papillomavirus E6 proteins is dependent on the integrity of the LXXLL binding motif.

Journal of Virology
Jennifer M SpangleK Münger

Abstract

The human papillomavirus (HPV) type 16 (HPV16) E6 protein can stimulate mechanistic target of rapamycin complex 1 (mTORC1) signaling and cap-dependent translation through activation of the PDK1 and mTORC2 kinases. Here we report that HPV18 E6 also enhances cap-dependent translation. The integrity of LXXLL and PDZ protein binding domains is important for activation of cap-dependent translation by high-risk mucosal HPV E6 proteins. Consistent with this model, low-risk mucosal HPV6b and HPV11 E6 proteins, which do not contain a PDZ protein binding motif, also activate cap-dependent translation and mTORC1, albeit at a lower efficiency than high-risk HPV E6 proteins. In contrast, cutaneous HPV5 and HPV8 E6 proteins, which lack LXXLL and PDZ motif protein binding, do not enhance cap-dependent translation. Mutagenic analyses of low-risk HPV E6 proteins revealed that association with the LXXLL motif containing ubiquitin ligase E6AP (UBE3A) correlates with activation of cap-dependent translation. Hence, activation of mTORC1 and cap-dependent translation may be important for the viral life cycle in specific epithelial tissue types and contribute to cellular transformation in cooperation with other biological activities of high-risk HPV E...Continue Reading

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Citations

Jan 23, 2016·Pathogens·Claire D James, Sally Roberts
Dec 6, 2014·Journal of Proteome Research·Jeffrey T GalliganPeter M Howley
May 29, 2013·Virology·Scott B Vande Pol, Aloysius J Klingelhutz
Sep 17, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·David G Pfister, Matthew G Fury
Sep 20, 2018·International Journal of Cancer. Journal International Du Cancer·Qiqi WangJunqi He
Jan 21, 2016·Proteomes·Haitham Sobhy
Sep 28, 2020·FEBS Open Bio·Vicente Morales-GarciaErick de la Cruz-Hernandez
Feb 10, 2018·Journal of Molecular Biology·Gustavo Martínez-NoëlPeter M Howley
Apr 24, 2021·Scientific Reports·Kana MiyaharaKeisuke Miyazawa
Oct 8, 2021·Proceedings of the National Academy of Sciences of the United States of America·Alejandra GarcíaGreco Hernández

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