RRC ID 54227
Author Funato K, Hayashi T, Echizen K, Negishi L, Shimizu N, Koyama-Nasu R, Nasu-Nishimura Y, Morishita Y, Tabar V, Todo T, Ino Y, Mukasa A, Saito N, Akiyama T.
Title SIRT2-mediated inactivation of p73 is required for glioblastoma tumorigenicity.
Journal EMBO Rep
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.
Volume 19(11)
Published 2018-11-1
DOI 10.15252/embr.201745587
PII embr.201745587
PMID 30213795
PMC PMC6216266
MeSH Acetylation Animals Apoptosis / drug effects Apoptosis / genetics Brain Neoplasms / metabolism Brain Neoplasms / pathology* Cell Proliferation Furans / pharmacology Gene Knockdown Techniques Glioblastoma / metabolism Glioblastoma / pathology* Humans Lysine / metabolism Mice, Nude Neoplastic Stem Cells / metabolism Neoplastic Stem Cells / pathology Quinolines / pharmacology Sirtuin 2 / antagonists & inhibitors Sirtuin 2 / genetics Sirtuin 2 / metabolism* Tumor Cells, Cultured Tumor Protein p73 / genetics Tumor Protein p73 / metabolism* Xenograft Model Antitumor Assays
IF 8.383
Times Cited 5
Resource
DNA material CS-RfA-CG (RDB04390) CS-RfA-CMV-mRFP1 (RDB05747) pENTR4-H1 (RDB04395) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394)