Author/Authors :
Mehta، نويسنده , , Shwetal and Huillard، نويسنده , , Emmanuelle and Kesari، نويسنده , , Santosh and Maire، نويسنده , , Cecile L. and Golebiowski، نويسنده , , Diane and Harrington، نويسنده , , Emily P. and Alberta، نويسنده , , John A. and Kane، نويسنده , , Michael F. and Theisen، نويسنده , , Matthew and Ligon، نويسنده , , Keith L. and Rowitch، نويسنده , , David H. and Stiles، نويسنده , , Charles D.، نويسنده ,
Abstract :
Summary
rade 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.
