The Human Adenovirus Type 5 E4orf6/E1B55K E3 Ubiquitin Ligase Complex Can Mimic E1A Effects on E2F

ABSTRACT The human adenovirus E4orf6/E1B55K E3 ubiquitin ligase is well known to promote viral replication by degrading an increasing number of cellular proteins that inhibit the efficient production of viral progeny. We report here a new function of the adenovirus 5 (Ad5) viral ligase complex that,...

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Autores principales:	Frédéric Dallaire, Sabrina Schreiner, G. Eric Blair, Thomas Dobner, Philip E. Branton, Paola Blanchette
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	adenovirus ubiquitin ligase E4orf6 E1B55K E1A Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/c01a38eed5be44cc8477ec767683e17f
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spelling	oai:doaj.org-article:c01a38eed5be44cc8477ec767683e17f2021-11-15T15:21:37ZThe Human Adenovirus Type 5 E4orf6/E1B55K E3 Ubiquitin Ligase Complex Can Mimic E1A Effects on E2F10.1128/mSphere.00014-152379-5042https://doaj.org/article/c01a38eed5be44cc8477ec767683e17f2016-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00014-15https://doaj.org/toc/2379-5042ABSTRACT The human adenovirus E4orf6/E1B55K E3 ubiquitin ligase is well known to promote viral replication by degrading an increasing number of cellular proteins that inhibit the efficient production of viral progeny. We report here a new function of the adenovirus 5 (Ad5) viral ligase complex that, although at lower levels, mimics effects of E1A products on E2F transcription factors. When expressed in the absence of E1A, the E4orf6 protein in complex with E1B55K binds E2F, disrupts E2F/retinoblastoma protein (Rb) complexes, and induces hyperphosphorylation of Rb, leading to induction of viral and cellular DNA synthesis as well as stimulation of early and late viral gene expression and production of viral progeny of E1/E3-defective adenovirus vectors. These new and previously undescribed functions of the E4orf6/E1B55K E3 ubiquitin ligase could play an important role in promoting the replication of wild-type viruses. IMPORTANCE During the course of work on the adenovirus E3 ubiquitin ligase formed by the viral E4orf6 and E1B55K proteins, we found, very surprisingly, that expression of these species was sufficient to permit low levels of replication of an adenovirus vector lacking E1A, the central regulator of infection. E1A products uncouple E2F transcription factors from Rb repression complexes, thus stimulating viral gene expression and cell and viral DNA synthesis. We found that the E4orf6/E1B55K ligase mimics these functions. This finding is of significance because it represents an entirely new function for the ligase in regulating adenovirus replication.Frédéric DallaireSabrina SchreinerG. Eric BlairThomas DobnerPhilip E. BrantonPaola BlanchetteAmerican Society for Microbiologyarticleadenovirusubiquitin ligaseE4orf6E1B55KE1AMicrobiologyQR1-502ENmSphere, Vol 1, Iss 1 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	adenovirus ubiquitin ligase E4orf6 E1B55K E1A Microbiology QR1-502
spellingShingle	adenovirus ubiquitin ligase E4orf6 E1B55K E1A Microbiology QR1-502 Frédéric Dallaire Sabrina Schreiner G. Eric Blair Thomas Dobner Philip E. Branton Paola Blanchette The Human Adenovirus Type 5 E4orf6/E1B55K E3 Ubiquitin Ligase Complex Can Mimic E1A Effects on E2F
description	ABSTRACT The human adenovirus E4orf6/E1B55K E3 ubiquitin ligase is well known to promote viral replication by degrading an increasing number of cellular proteins that inhibit the efficient production of viral progeny. We report here a new function of the adenovirus 5 (Ad5) viral ligase complex that, although at lower levels, mimics effects of E1A products on E2F transcription factors. When expressed in the absence of E1A, the E4orf6 protein in complex with E1B55K binds E2F, disrupts E2F/retinoblastoma protein (Rb) complexes, and induces hyperphosphorylation of Rb, leading to induction of viral and cellular DNA synthesis as well as stimulation of early and late viral gene expression and production of viral progeny of E1/E3-defective adenovirus vectors. These new and previously undescribed functions of the E4orf6/E1B55K E3 ubiquitin ligase could play an important role in promoting the replication of wild-type viruses. IMPORTANCE During the course of work on the adenovirus E3 ubiquitin ligase formed by the viral E4orf6 and E1B55K proteins, we found, very surprisingly, that expression of these species was sufficient to permit low levels of replication of an adenovirus vector lacking E1A, the central regulator of infection. E1A products uncouple E2F transcription factors from Rb repression complexes, thus stimulating viral gene expression and cell and viral DNA synthesis. We found that the E4orf6/E1B55K ligase mimics these functions. This finding is of significance because it represents an entirely new function for the ligase in regulating adenovirus replication.
format	article
author	Frédéric Dallaire Sabrina Schreiner G. Eric Blair Thomas Dobner Philip E. Branton Paola Blanchette
author_facet	Frédéric Dallaire Sabrina Schreiner G. Eric Blair Thomas Dobner Philip E. Branton Paola Blanchette
author_sort	Frédéric Dallaire
title	The Human Adenovirus Type 5 E4orf6/E1B55K E3 Ubiquitin Ligase Complex Can Mimic E1A Effects on E2F
title_short	The Human Adenovirus Type 5 E4orf6/E1B55K E3 Ubiquitin Ligase Complex Can Mimic E1A Effects on E2F
title_full	The Human Adenovirus Type 5 E4orf6/E1B55K E3 Ubiquitin Ligase Complex Can Mimic E1A Effects on E2F
title_fullStr	The Human Adenovirus Type 5 E4orf6/E1B55K E3 Ubiquitin Ligase Complex Can Mimic E1A Effects on E2F
title_full_unstemmed	The Human Adenovirus Type 5 E4orf6/E1B55K E3 Ubiquitin Ligase Complex Can Mimic E1A Effects on E2F
title_sort	human adenovirus type 5 e4orf6/e1b55k e3 ubiquitin ligase complex can mimic e1a effects on e2f
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/c01a38eed5be44cc8477ec767683e17f
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The Human Adenovirus Type 5 E4orf6/E1B55K E3 Ubiquitin Ligase Complex Can Mimic E1A Effects on E2F

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