TY - JOUR
T1 - KSHV latent protein LANA2 inhibits sumo2 modification of p53
AU - Laura, Marcos Villar
AU - De La Cruz-Herrera, Carlos F.
AU - Ferreirós, Alba
AU - Baz-Martínez, Maite
AU - Lang, Valerie
AU - Vidal, Anxo
AU - Muñoz-Fontela, Cesar
AU - Rodríguez, Manuel S.
AU - Collado, Manuel
AU - Rivas, Carmen
N1 - Publisher Copyright:
© 2015 Taylor & Francis Group, LLC.
PY - 2015/1/15
Y1 - 2015/1/15
N2 - 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.
AB - 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.
KW - KSHV
KW - LANA2
KW - P53
KW - SUMO
KW - Senescence
UR - http://www.scopus.com/inward/record.url?scp=84926675227&partnerID=8YFLogxK
U2 - 10.4161/15384101.2014.980657
DO - 10.4161/15384101.2014.980657
M3 - Article
C2 - 25607652
AN - SCOPUS:84926675227
SN - 1538-4101
VL - 14
SP - 277
EP - 282
JO - Cell Cycle
JF - Cell Cycle
IS - 2
ER -