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.

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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