Title

The Central Nervous System-Restricted Transcription Factor Olig2 Opposes p53 Responses to Genotoxic Damage in Neural Progenitors and Malignant Glioma

Document Type

Article

Abstract

High-grade gliomas are notoriously insensitive to radiation and genotoxic drugs. Paradoxically, the p53 gene is structurally intact in the majority of these tumors. Resistance to genotoxic modalities in p53-positive gliomas is generally attributed to attenuation of p53 functions by mutations of other components within the p53 signaling axis, such as p14Arf, MDM2, and ATM, but this explanation is not entirely satisfactory. We show here that the central nervous system (CNS)-restricted transcription factor Olig2 affects a key posttranslational modification of p53 in both normal and malignant neural progenitors and thereby antagonizes the interaction of p53 with promoter elements of multiple target genes. In the absence of Olig2 function, even attenuated levels of p53 are adequate for biological responses to genotoxic damage. © 2011 Elsevier Inc.

Publication Date

1-1-2011

Publication Title

Cancer Cell

ISSN

15356108

E-ISSN

18783686

Volume

19

Issue

3

First Page

359

Last Page

371

PubMed ID

21397859

Digital Object Identifier (DOI)

10.1016/j.ccr.2011.01.035

Share

COinS