Deubiquitinating function of adenovirus proteinase.
The invasion strategy of many viruses involves the synthesis of viral gene products that mimic the functions of the cellular proteins and thus interfere with the key cellular processes. Here we show that adenovirus infection is accompanied by an increased ubiquitin-cleaving (deubiquitinating) activity in the host cells. Affinity chromatography on ubiquitin aldehyde (Ubal), which was designed to identify the deubiquitinating proteases, revealed the presence of adenovirus L3 23K proteinase (Avp) in the eluate from adenovirus-infected cells. This proteinase is known to be necessary for the processing of viral precursor proteins during virion maturation. We show here that in vivo Avp deubiquitinates a number of cellular proteins. Analysis of the substrate specificity of Avp in vitro demonstrated that the protein deubiquitination by this enzyme could be as efficient as proteolytic processing of viral proteins. The structural model of the Ubal-Avp interaction revealed some similarity between S1-S4 substrate binding sites of Avp and ubiquitin hydrolases. These results may reflect the acquisition of an advantageous property by adenovirus and may indicate the importance of ubiquitin pathways in viral infection.
Balakirev
Maxim Y
MY
Institut de Biologie Structurale, Grenoble 38027. Département de Biologie Moléculaire et Structurale, CEA, Grenoble 38054, France. maxbala@ibs.fr
Jaquinod
Michel
M
Haas
Arthur L
AL
Chroboczek
Jadwiga
J
D000260:Adenoviruses, Human / Q000201:enzymology* / Q000472:pathogenicity; D000595:Amino Acid Sequence; D002846:Chromatography, Affinity; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011480:Protease Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D013379:Substrate Specificity; D014452:Ubiquitins / Q000378:metabolism*
D011480:Protease Inhibitors; D011506:Proteins; D014452:Ubiquitins; D003546:Cysteine Endopeptidases; C091827:adenain