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

Publication ,  Journal Article
Bell, RJA; Rube, HT; Kreig, A; Mancini, A; Fouse, SD; Nagarajan, RP; Choi, S; Hong, C; He, D; Pekmezci, M; Wiencke, JK; Wrensch, MR; Myong, S ...
Published in: Science
May 29, 2015

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.

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Published In

Science

DOI

EISSN

1095-9203

Publication Date

May 29, 2015

Volume

348

Issue

6238

Start / End Page

1036 / 1039

Location

United States

Related Subject Headings

  • Telomerase
  • Protein Multimerization
  • Protein Binding
  • Promoter Regions, Genetic
  • Humans
  • Glioblastoma
  • General Science & Technology
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Regulation, Enzymologic
  • GA-Binding Protein Transcription Factor
 

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Bell, R. J. A., Rube, H. T., Kreig, A., Mancini, A., Fouse, S. D., Nagarajan, R. P., … Costello, J. F. (2015). Cancer. The transcription factor GABP selectively binds and activates the mutant TERT promoter in cancer. Science, 348(6238), 1036–1039. https://doi.org/10.1126/science.aab0015
Bell, Robert J. A., H Tomas Rube, Alex Kreig, Andrew Mancini, Shaun D. Fouse, Raman P. Nagarajan, Serah Choi, et al. “Cancer. The transcription factor GABP selectively binds and activates the mutant TERT promoter in cancer.Science 348, no. 6238 (May 29, 2015): 1036–39. https://doi.org/10.1126/science.aab0015.
Bell RJA, Rube HT, Kreig A, Mancini A, Fouse SD, Nagarajan RP, et al. Cancer. The transcription factor GABP selectively binds and activates the mutant TERT promoter in cancer. Science. 2015 May 29;348(6238):1036–9.
Bell, Robert J. A., et al. “Cancer. The transcription factor GABP selectively binds and activates the mutant TERT promoter in cancer.Science, vol. 348, no. 6238, May 2015, pp. 1036–39. Pubmed, doi:10.1126/science.aab0015.
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. Cancer. The transcription factor GABP selectively binds and activates the mutant TERT promoter in cancer. Science. 2015 May 29;348(6238):1036–1039.
Journal cover image

Published In

Science

DOI

EISSN

1095-9203

Publication Date

May 29, 2015

Volume

348

Issue

6238

Start / End Page

1036 / 1039

Location

United States

Related Subject Headings

  • Telomerase
  • Protein Multimerization
  • Protein Binding
  • Promoter Regions, Genetic
  • Humans
  • Glioblastoma
  • General Science & Technology
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Regulation, Enzymologic
  • GA-Binding Protein Transcription Factor