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Updated: Feb 5, 2026

Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates
Published on: February 27, 2016
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.
Abstract:
Glioblastoma is one of the most aggressive forms of cancers and has a poor prognosis. Genomewide analyses have revealed that a set of core signaling pathways, the p53, RB, and RTK pathways, are commonly deregulated in glioblastomas. However, the molecular mechanisms underlying the tumorigenicity of glioblastoma are not fully understood. Here, we show that the lysine deacetylase SIRT2 is required for the proliferation and tumorigenicity of glioblastoma cells, including glioblastoma stem cells. Furthermore, we demonstrate that SIRT2 regulates p73 transcriptional activity by deacetylation of its C-terminal lysine residues. Our results suggest that SIRT2-mediated inactivation of p73 is critical for the proliferation and tumorigenicity of glioblastoma cells and that SIRT2 may be a promising molecular target for the therapy of glioblastoma.
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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