SIRT2‐mediated inactivation of p73 is required for glioblastoma tumorigenicity

• Published in: EMBO reports Vol. 19; no. 11
• Main Authors: Funato, Kosuke, Hayashi, Tomoatsu, Echizen, Kanae, Negishi, Lumi, Shimizu, Naomi, Koyama‐Nasu, Ryo, Nasu‐Nishimura, Yukiko, Morishita, Yasuyuki, Tabar, Viviane, Todo, Tomoki, Ino, Yasushi, Mukasa, Akitake, Saito, Nobuhito, Akiyama, Tetsu
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.11.2018; John Wiley and Sons Inc
• Subjects: Brain cancer; cancer stem cells; Cell proliferation; Deacetylation; Deactivation; Deregulation; Glioblastoma; Glioblastoma cells; Inactivation; Lysine; Molecular modelling; p53 Protein; p73; Scientific Report; Scientific Reports; SIRT2; Stem cells; Transcription; Tumor suppressor genes; Tumorigenicity; Tumors; glioblastoma; cancer stem cells; p73; SIRT2
• ISSN: 1469-221X; 1469-3178
• DOI: 10.15252/embr.201745587

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. Synopsis SIRT2 targets the tumor suppressor p73, thereby deacetylating its C‐terminus and suppressing its transcriptional activity. SIRT2‐mediated inactivation of p73 is crucial for the tumorigenicity of glioblastoma cells. The lysine deacetylase SIRT2 is required for the proliferation and tumorigenicity of glioblastoma cells. SIRT2 targets and regulates the transcriptional activity of the tumor suppressor p73. SIRT2‐mediated inactivation of p73 is critical for the proliferation and tumorigenicity of glioblastoma cells. SIRT2 targets the tumor suppressor p73, thereby deacetylating its C‐terminus and suppressing its transcriptional activity. SIRT2‐mediated inactivation of p73 is crucial for the tumorigenicity of glioblastoma cells.