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
Recommended Citation
Mehta, Shwetal; Huillard, Emmanuelle; Kesari, Santosh; Maire, Cecile L.; Golebiowski, Diane; Harrington, Emily P.; Alberta, John A.; Kane, Michael F.; Theisen, Matthew; Ligon, Keith L.; Rowitch, David H.; and Stiles, Charles D., "The Central Nervous System-Restricted Transcription Factor Olig2 Opposes p53 Responses to Genotoxic Damage in Neural Progenitors and Malignant Glioma" (2011). Translational Neuroscience. 1609.
https://scholar.barrowneuro.org/neurobiology/1609