期刊
PROTEOMICS
卷 16, 期 3, 页码 417-426出版社
WILEY
DOI: 10.1002/pmic.201500327
关键词
Biomedicine; Melanoma; Telomerase; Transcription
资金
- DevCom FP7 Marie Curie ITN
- Division of Cancer Epidemiology and Genetics
- National Cancer Institute
- National Institutes of Health
Aberrant telomerase reactivation in differentiated cells represents a major event in oncogenic transformation. Recurrent somatic mutations in the human telomerase reverse transcriptase (TERT) promoter region, predominantly localized to two nucleotide positions, are highly prevalent in many cancer types. Both mutations create novel consensus E26 transformation-specific (ETS) motifs and are associated with increased TERT expression. Here, we perform an unbiased proteome-wide survey of transcription factor binding at TERT promoter mutations in melanoma. We observe ELF1 binding at both mutations in vitro and we show that increased recruitment of GABP is enabled by the spatial architecture of native and novel ETS motifs in the TERT promoter region. We characterize the dynamics of competitive binding between ELF1 and GABP and provide evidence for ELF1 exclusion by transcriptionally active GABP. This study thus provides an important description of proteome-wide, mutation-specific binding at the recurrent, oncogenic TERT promoter mutations.
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