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

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


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 languageEnglish
Pages (from-to)149-158
Number of pages10
Issue number2
Publication statusPublished - 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.


  • Adenovirus E1A
  • Immunoproteasome
  • MECL1


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