Adenovirus E1A interacts directly with, and regulates the level of expression of, the immunoproteasome component MECL1.
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.
Cancer Research UK, School of Cancer Sciences, University of Birmingham, Birmingham B15 2TT, UK.
Sarah
S
Berhane
Cristina
C
Aresté
Jailal N
JN
Ablack
Gordon B
GB
Ryan
David J
DJ
Blackbourn
Joe S
JS
Mymryk
Andrew S
AS
Turnell
Jane C
JC
Steele
Roger J A
RJ
Grand
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D017500:Adenovirus E1A Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000096:biosynthesis / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
D017500:Adenovirus E1A Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C071313:LMP-2 protein; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; C098948:PSMB10 protein, human; D046988:Proteasome Endopeptidase Complex