Abstract:
: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.
journal_name
Proteomicsjournal_title
Proteomicsauthors
Makowski MM,Willems E,Fang J,Choi J,Zhang T,Jansen PW,Brown KM,Vermeulen Mdoi
10.1002/pmic.201500327subject
Has Abstractpub_date
2016-02-01 00:00:00pages
417-26issue
3eissn
1615-9853issn
1615-9861journal_volume
16pub_type
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