title: KSHV latent protein LANA2 inhibits sumo2 modification of p53.
abstract: Tumor suppressor p53 plays a crucial antiviral role and targeting of p53 by viral proteins is a common mechanism involved in virus oncogenesis. The activity of p53 is tightly regulated at the post-translational levels through a myriad of modifications. Among them, modification of p53 by SUMO has been associated with the onset of cellular senescence. Kaposi´s sarcoma-associated herpesvirus (KSHV) expresses several proteins targeting p53, including the latent protein LANA2 that regulates polyubiquitylation and phosphorylation of p53. Here we show that LANA2 also inhibits the modification of p53 by SUMO2. Furthermore, we show that the reduction of p53-SUMO2 conjugation by LANA2, as well as the p53-LANA2 interaction, both require the SUMOylation of the viral protein and its interaction with SUMO or SUMOylated proteins in a non-covalent manner. Finally, we show that the control of p53-SUMO2 conjugation by LANA2 correlates with its ability to inhibit SUMO2- and type I interferon-induced senescence. These results highlight the importance of p53 SUMOylation in the control of virus infection and suggest that viral oncoproteins could contribute to viral infection and cell transformation by abrogating p53 SUMOylation.
authors.affiliation: a Department of Molecular and Cellular Biology; Centro Nacional de Biotecnología-CSIC ; Madrid , Spain.
authors.forename: Marcos-Villar
authors.initials: MV
authors.lastname: Laura
authors.forename: Carlos F
authors.initials: CF
authors.lastname: de la Cruz-Herrera
authors.forename: Alba
authors.initials: A
authors.lastname: Ferreirós
authors.forename: Maite
authors.initials: M
authors.lastname: Baz-Martínez
authors.forename: Valerie
authors.initials: V
authors.lastname: Lang
authors.forename: Anxo
authors.initials: A
authors.lastname: Vidal
authors.forename: Cesar
authors.initials: C
authors.lastname: Muñoz-Fontela
authors.forename: Manuel S
authors.initials: MS
authors.lastname: Rodríguez
authors.forename: Manuel
authors.initials: M
authors.lastname: Collado
authors.forename: Carmen
authors.initials: C
authors.lastname: Rivas
mesh_terms: D000956:Antigens, Viral / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D019288:Herpesvirus 8, Human / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism*; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D000956:Antigens, Viral; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; C117909:SUMO2 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins; C109540:latency-associated nuclear antigen; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9
keywords: KSHV; LANA2; SUMO; p53; senescence