Adenovirus E1A interacts directly with, and regulates the level of expression of, the immunoproteasome component MECL1

Sarah Berhane; Cristina Aresté; Jailal N. Ablack; Gordon B. Ryan; David J. Blackbourn; Joe S. Mymryk; Andrew S. Turnell; Jane C. Steele; Roger J.A. Grand

doi:10.1016/j.virol.2011.09.025

Adenovirus E1A interacts directly with, and regulates the level of expression of, the immunoproteasome component MECL1

Sarah Berhane, Cristina Aresté, Jailal N. Ablack, Gordon B. Ryan, David J. Blackbourn, Joe S. Mymryk, Andrew S. Turnell, Jane C. Steele, Roger J.A. Grand^*

^*Corresponding author for this work

Medical Sciences

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

Abstract

Proteasomes represent the major non-lysosomal mechanism responsible for the degradation of proteins. Following interferon γ treatment 3 proteasome subunits are replaced producing immunoproteasomes. Adenovirus E1A interacts with components of the 20S and 26S proteasome and can affect presentation of peptides. In light of these observations we investigated the relationship of AdE1A to the immunoproteasome. AdE1A interacts with the immunoproteasome subunit, MECL1. In contrast, AdE1A binds poorly to the proteasome β2 subunit which is replaced by MECL1 in the conversion of proteasomes to immunoproteasomes. Binding sites on E1A for MECL1 correspond to the N-terminal region and conserved region 3. Furthermore, AdE1A causes down-regulation of MECL1 expression, as well as LMP2 and LMP7, induced by interferon γ treatment during Ad infections or following transient transfection. Consistent with previous reports AdE1A reduced IFNγ-stimulated STAT1 phosphorylation which appeared to be responsible for its ability to reduce expression of immunoproteasome subunits.

Original language	English
Pages (from-to)	149-158
Number of pages	10
Journal	Virology
Volume	421
Issue number	2
DOIs	https://doi.org/10.1016/j.virol.2011.09.025
Publication status	Published - 20 Dec 2011

Bibliographical note

Funding Information:
We are most grateful to Gavin Wilkinson, Rich Stanton and Brian McSharry for the gift of the Ad5ΔE3 virus and Elke Krüger, Ulrike Kuckelkorn and Marcus Groettrup for the gift of constructs and antibodies. We also thank the University of Birmingham College of Medicine and Dentistry for funding to SB. We also thank Medical Research Council and Cancer Research UK (to D. J. B.) for funding.

Keywords

Adenovirus E1A
Immunoproteasome
MECL1

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10.1016/j.virol.2011.09.025

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title = "Adenovirus E1A interacts directly with, and regulates the level of expression of, the immunoproteasome component MECL1",

abstract = "Proteasomes represent the major non-lysosomal mechanism responsible for the degradation of proteins. Following interferon γ treatment 3 proteasome subunits are replaced producing immunoproteasomes. Adenovirus E1A interacts with components of the 20S and 26S proteasome and can affect presentation of peptides. In light of these observations we investigated the relationship of AdE1A to the immunoproteasome. AdE1A interacts with the immunoproteasome subunit, MECL1. In contrast, AdE1A binds poorly to the proteasome β2 subunit which is replaced by MECL1 in the conversion of proteasomes to immunoproteasomes. Binding sites on E1A for MECL1 correspond to the N-terminal region and conserved region 3. Furthermore, AdE1A causes down-regulation of MECL1 expression, as well as LMP2 and LMP7, induced by interferon γ treatment during Ad infections or following transient transfection. Consistent with previous reports AdE1A reduced IFNγ-stimulated STAT1 phosphorylation which appeared to be responsible for its ability to reduce expression of immunoproteasome subunits.",

keywords = "Adenovirus E1A, Immunoproteasome, MECL1",

author = "Sarah Berhane and Cristina Arest{\'e} and Ablack, {Jailal N.} and Ryan, {Gordon B.} and Blackbourn, {David J.} and Mymryk, {Joe S.} and Turnell, {Andrew S.} and Steele, {Jane C.} and Grand, {Roger J.A.}",

note = "Funding Information: We are most grateful to Gavin Wilkinson, Rich Stanton and Brian McSharry for the gift of the Ad5ΔE3 virus and Elke Kr{\"u}ger, Ulrike Kuckelkorn and Marcus Groettrup for the gift of constructs and antibodies. We also thank the University of Birmingham College of Medicine and Dentistry for funding to SB. We also thank Medical Research Council and Cancer Research UK (to D. J. B.) for funding.",

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AU - Berhane, Sarah

AU - Aresté, Cristina

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AU - Ryan, Gordon B.

AU - Blackbourn, David J.

AU - Mymryk, Joe S.

AU - Turnell, Andrew S.

AU - Steele, Jane C.

AU - Grand, Roger J.A.

N1 - Funding Information: We are most grateful to Gavin Wilkinson, Rich Stanton and Brian McSharry for the gift of the Ad5ΔE3 virus and Elke Krüger, Ulrike Kuckelkorn and Marcus Groettrup for the gift of constructs and antibodies. We also thank the University of Birmingham College of Medicine and Dentistry for funding to SB. We also thank Medical Research Council and Cancer Research UK (to D. J. B.) for funding.

PY - 2011/12/20

Y1 - 2011/12/20

N2 - Proteasomes represent the major non-lysosomal mechanism responsible for the degradation of proteins. Following interferon γ treatment 3 proteasome subunits are replaced producing immunoproteasomes. Adenovirus E1A interacts with components of the 20S and 26S proteasome and can affect presentation of peptides. In light of these observations we investigated the relationship of AdE1A to the immunoproteasome. AdE1A interacts with the immunoproteasome subunit, MECL1. In contrast, AdE1A binds poorly to the proteasome β2 subunit which is replaced by MECL1 in the conversion of proteasomes to immunoproteasomes. Binding sites on E1A for MECL1 correspond to the N-terminal region and conserved region 3. Furthermore, AdE1A causes down-regulation of MECL1 expression, as well as LMP2 and LMP7, induced by interferon γ treatment during Ad infections or following transient transfection. Consistent with previous reports AdE1A reduced IFNγ-stimulated STAT1 phosphorylation which appeared to be responsible for its ability to reduce expression of immunoproteasome subunits.

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KW - Adenovirus E1A

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Adenovirus E1A interacts directly with, and regulates the level of expression of, the immunoproteasome component MECL1

Abstract

Bibliographical note

Keywords

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