SIRT2-mediated inactivation of p73 is required for glioblastoma tumorigenicity

Kosuke Funato1,2, Tomoatsu Hayashi1, Kanae Echizen1

  • 1Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.

EMBO Reports
|September 15, 2018
PubMed

Insights

SIRT2 is essential for glioblastoma cell growth and survival. Inhibiting SIRT2 may offer a new therapeutic strategy for glioblastoma, a highly aggressive brain cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Glioblastoma is a highly aggressive brain cancer with poor patient outcomes.
  • Key signaling pathways like p53, RB, and RTK are frequently altered in glioblastomas.
  • The precise molecular drivers of glioblastoma tumorigenicity remain incompletely understood.

Purpose of the Study:

  • To investigate the role of lysine deacetylase SIRT2 in glioblastoma.
  • To determine if SIRT2 is essential for glioblastoma cell proliferation and tumorigenicity.
  • To explore the molecular mechanisms by which SIRT2 influences glioblastoma.

Main Methods:

  • Assessed the requirement of SIRT2 for glioblastoma cell and glioblastoma stem cell proliferation.
  • Investigated SIRT2's effect on p73 transcriptional activity.
  • Analyzed SIRT2-mediated deacetylation of p73's C-terminal lysine residues.

Main Results:

  • SIRT2 is indispensable for the proliferation and tumorigenicity of glioblastoma cells, including stem cells.
  • SIRT2 directly regulates p73 transcriptional activity.
  • SIRT2 inactivates p73 through deacetylation of its C-terminal lysine residues.

Conclusions:

  • SIRT2-mediated inactivation of p73 is crucial for glioblastoma cell proliferation and tumorigenicity.
  • SIRT2 represents a potential therapeutic target for glioblastoma treatment.
  • Targeting SIRT2 could offer a novel strategy against this aggressive cancer.

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