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Updated: Apr 18, 2026

In Vitro SUMOylation Assay to Study SUMO E3 Ligase Activity
Published on: January 29, 2018
KSHV latent protein LANA2 inhibits sumo2 modification of p53
Marcos-Villar Laura1, Carlos F de la Cruz-Herrera, Alba Ferreirós
1a Department of Molecular and Cellular Biology; Centro Nacional de Biotecnología-CSIC ; Madrid , Spain.
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.
Insights
Kaposi´s sarcoma-associated herpesvirus LANA2 protein inhibits p53 SUMOylation, a modification crucial for antiviral defense and preventing senescence. This viral targeting of p53 SUMOylation may promote viral infection and cell transformation.
Area of Science:
- Molecular Biology
- Virology
- Oncology
Background:
- Tumor suppressor p53 is vital for antiviral responses and its regulation involves post-translational modifications like SUMOylation.
- Viral proteins often target p53 to promote oncogenesis, with Kaposi´s sarcoma-associated herpesvirus (KSHV) LANA2 known to affect p53 ubiquitylation and phosphorylation.
Purpose of the Study:
- To investigate the effect of KSHV LANA2 on p53 SUMOylation.
- To elucidate the mechanism by which LANA2 influences p53 SUMOylation and its role in cellular senescence.
Main Methods:
- Assays to detect p53-SUMO2 conjugation and p53-LANA2 interaction.
- Experiments to assess the requirement of LANA2 SUMOylation and its interaction with SUMOylated proteins.
- Analysis of LANA2's effect on SUMO2- and type I interferon-induced senescence.
Main Results:
- KSHV LANA2 was shown to inhibit the SUMOylation of p53 by SUMO2.
- LANA2's inhibition of p53 SUMOylation and its interaction with p53 depend on LANA2's own SUMOylation and non-covalent interaction with SUMO or SUMOylated proteins.
- LANA2's control over p53 SUMO2 conjugation correlated with its ability to suppress SUMO2- and type I interferon-induced senescence.
Conclusions:
- p53 SUMOylation is critical for controlling viral infections.
- Viral oncoproteins, like KSHV LANA2, may facilitate viral infection and cell transformation by disrupting p53 SUMOylation.
- Targeting p53 SUMOylation represents a novel mechanism for viral pathogenesis.
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