title: Regulation of vaccinia virus E3 protein by small ubiquitin-like modifier proteins.
abstract: The vaccinia virus (VACV) E3 protein is essential for virulence and has antiapoptotic activity and the ability to impair the host innate immune response. Here we demonstrate that E3 interacts with SUMO1 through a small ubiquitin-like modifier (SUMO)-interacting motif (SIM). SIM integrity is required for maintaining the stability of the viral protein and for the covalent conjugation of E3 to SUMO1 or SUMO2, a modification that has a negative effect on the E3 transcriptional transactivation of the p53-upregulated modulator of apoptosis (PUMA) and APAF-1 genes. We also demonstrate that E3 is ubiquitinated, a modification that does not destabilize the wild-type protein but triggers the degradation of an E3-ΔSIM mutant. This report constitutes the first demonstration of the important roles that both SUMO and ubiquitin play in the regulation of the VACV protein E3.
authors.affiliation: Centro Nacional de Biotecnología, CSIC, Campus Universidad Autónoma de Madrid, Madrid 28049, Spain.
authors.forename: José
authors.initials: J
authors.lastname: González-Santamaría
authors.forename: Michela
authors.initials: M
authors.lastname: Campagna
authors.forename: María Angel
authors.initials: MA
authors.lastname: García
authors.forename: Laura
authors.initials: L
authors.lastname: Marcos-Villar
authors.forename: Dolores
authors.initials: D
authors.lastname: González
authors.forename: Pedro
authors.initials: P
authors.lastname: Gallego
authors.forename: Fernando
authors.initials: F
authors.lastname: Lopitz-Otsoa
authors.forename: Susana
authors.initials: S
authors.lastname: Guerra
authors.forename: Manuel S
authors.initials: MS
authors.lastname: Rodríguez
authors.forename: Mariano
authors.initials: M
authors.lastname: Esteban
authors.forename: Carmen
authors.initials: C
authors.lastname: Rivas
mesh_terms: D002460:Cell Line; D015536:Down-Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D011485:Protein Binding; D025941:Protein Interaction Mapping; D016601:RNA-Binding Proteins / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D054875:Ubiquitination; D014616:Vaccinia virus / Q000276:immunology*; D014764:Viral Proteins / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: C081374:E3L protein, Vaccinia virus; D016601:RNA-Binding Proteins; D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; C117909:SUMO2 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D014764:Viral Proteins; D037521:Virulence Factors