articleScienceMay 14, 2015GREEN OA

The transcription factor GABP selectively binds and activates the mutant TERT promoter in cancer

University of California, San Francisco · Neurological Surgery · +1 more institution

PubMed
Indexed incrossrefpubmed

Abstract

Reactivation of telomerase reverse transcriptase (TERT) expression enables cells to overcome replicative senescence and escape apoptosis, which are fundamental steps in the initiation of human cancer. Multiple cancer types, including up to 83% of glioblastomas (GBMs), harbor highly recurrent TERT promoter mutations of unknown function but specific to two nucleotide positions. We identified the functional consequence of these mutations in GBMs to be recruitment of the multimeric GA-binding protein (GABP) transcription factor specifically to the mutant promoter. Allelic recruitment of GABP is consistently observed across four cancer types, highlighting a shared mechanism underlying TERT reactivation. Tandem…

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