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

Published

Journal Article

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 flanking native E26 transformation-specific motifs critically cooperate with these mutations to activate TERT, probably by facilitating GABP heterotetramer binding. GABP thus directly links TERT promoter mutations to aberrant expression in multiple cancers.

Full Text

Duke Authors

Cited Authors

  • Bell, RJA; Rube, HT; Kreig, A; Mancini, A; Fouse, SD; Nagarajan, RP; Choi, S; Hong, C; He, D; Pekmezci, M; Wiencke, JK; Wrensch, MR; Chang, SM; Walsh, KM; Myong, S; Song, JS; Costello, JF

Published Date

  • May 29, 2015

Published In

Volume / Issue

  • 348 / 6238

Start / End Page

  • 1036 - 1039

PubMed ID

  • 25977370

Pubmed Central ID

  • 25977370

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.aab0015

Language

  • eng

Conference Location

  • United States