Mechanism of Adenovirus E4-ORF3-Mediated SUMO Modifications

MBio
Sook-Young Sohn, Patrick Hearing

Abstract

Regulation of a variety of different cellular processes, including posttranslational modifications, is critical for the ability of many viruses to replicate efficiently within host cells. The adenovirus (Ad) E4-ORF3 protein assembles into polymers and forms a unique nuclear scaffold that leads to the relocalization and sequestration of cellular proteins, including small ubiquitin-like modifiers (SUMOs). Previously, we showed that E4-ORF3 functions as a SUMO E3 ligase of transcriptional intermediary factor-1 gamma (TIF-1γ) and promotes poly-SUMO chain formation. Here, we present cellular and biochemical data to further understand E4-ORF3 SUMO ligase activity. E4-ORF3 proteins from five different Ad species were found to possess SUMO E3 ligase activities in vitro In infected cells, SUMO modifications of target proteins occurred only when the proteins were recruited into E4-ORF3 polymeric structures. By analyzing SUMO-deficient TIF-1γ, we demonstrated that SUMO conjugations are not required for E4-ORF3-mediated relocalization of target proteins in infected cells, implying that sequestration is followed by SUMO modification. In vitro SUMO conjugation assays revealed the Ad E1B-55K oncoprotein as a new viral target of E4-ORF3-mediat...Continue Reading

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Citations

Nov 14, 2019·FEBS Letters·Sook-Young Sohn, Patrick Hearing
Dec 29, 2020·Virus Research·Samuel HofmannSabrina Schreiner
Jan 22, 2022·Advanced Science·Yao FanFangfang Zhou

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Methods Mentioned

BETA
fluorescence microscopy
pulldown
coimmunoprecipitation
transfection

Software Mentioned

NIS
. Fr
AxioVision
Phylogeny
Elements

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