SIRT2-mediated inactivation of p73 is required for glioblastoma tumorigenicity

Kosuke Funato; Tomoatsu Hayashi; Kanae Echizen; Lumi Negishi; Naomi Shimizu; Ryo Koyama-Nasu; Yukiko Nasu-Nishimura; Yasuyuki Morishita; Viviane Tabar; Tomoki Todo; Yasushi Ino; Akitake Mukasa; Nobuhito Saito; Tetsu Akiyama

doi:10.15252/embr.201745587

SIRT2-mediated inactivation of p73 is required for glioblastoma tumorigenicity

Kosuke Funato, Tomoatsu Hayashi, Kanae Echizen, Lumi Negishi, Naomi Shimizu, Ryo Koyama-Nasu, Yukiko Nasu-Nishimura, Yasuyuki Morishita, Viviane Tabar, Tomoki Todo, Yasushi Ino, Akitake Mukasa, Nobuhito Saito, Tetsu Akiyama

Research output: Contribution to journal › Article › peer-review

42 Scopus citations

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.

Original language	English
Article number	e45587
Journal	EMBO Reports
Volume	19
Issue number	11
DOIs	https://doi.org/10.15252/embr.201745587
State	Published - Nov 2018
Externally published	Yes

Keywords

cancer stem cells
glioblastoma
p73
SIRT2

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.15252/embr.201745587

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title = "SIRT2-mediated inactivation of p73 is required for glioblastoma tumorigenicity",

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.",

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doi = "10.15252/embr.201745587",

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T1 - SIRT2-mediated inactivation of p73 is required for glioblastoma tumorigenicity

AU - Funato, Kosuke

AU - Hayashi, Tomoatsu

AU - Echizen, Kanae

AU - Negishi, Lumi

AU - Shimizu, Naomi

AU - Koyama-Nasu, Ryo

AU - Nasu-Nishimura, Yukiko

AU - Morishita, Yasuyuki

AU - Tabar, Viviane

AU - Todo, Tomoki

AU - Ino, Yasushi

AU - Mukasa, Akitake

AU - Saito, Nobuhito

AU - Akiyama, Tetsu

PY - 2018/11

Y1 - 2018/11

N2 - 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.

AB - 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.

KW - cancer stem cells

KW - glioblastoma

KW - p73

KW - SIRT2

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U2 - 10.15252/embr.201745587

DO - 10.15252/embr.201745587

M3 - 記事

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AN - SCOPUS:85053438571

SN - 1469-221X

VL - 19

JO - EMBO Reports

JF - EMBO Reports

IS - 11

M1 - e45587

ER -

SIRT2-mediated inactivation of p73 is required for glioblastoma tumorigenicity

Abstract

Keywords

UN SDGs

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