Table 1 -.

Regulation of the mutant TERT promoter by ETS transcription factors

Trans-acting factor	Cell type	Reference	Notes
GABP	Glioblastoma	[18]	GABPA knockdown suppressed TERT expression/activity. GABPA binding to mutant TERT promoter also identified in melanoma, hepatocellular carcinoma and neuroblastoma cell lines.
	Glioblastoma	[104]	Disruption of tetramer-forming GABPB1L isoform depleted TERT expression, leading to telomere shortening and loss of replicative immortality.
	Melanoma	[123]	GABP binding to mutant TERT promoter excluded ELF1, promoting TERT expression.
	Melanoma & glioblastoma	[101]	CRISPR reversion of TPMs to wildtype suppressed GABPA binding and TERT expression in isogenic cell lines.
	Thyroid cancer & melanoma	[121]	BRAFmut. MAPK activation of FOS enhanced GABPB expression, GABP recruitment to mutant TERT promoter, and TERT expression.
	Thyroid cancer	[124]	GABPA knockdown suppressed TERT in TERT promoter mutant and wildtype cells.
ETS1	Melanoma	[102]	BRAFmut. MEK inhibition suppressed phospho-ETS1 (Thr38) and TERT expression/activity.
	Glioma	[125]	BRAFmut. BRAF inhibition attenuated TERT expression/activity.
	Glioblastoma	[103]	ETS1/2, in cooperation with non-canonical NF-κB signalling, enhanced TERT expression/activity selectively in cells with C250T, but not C228T TERT promoter mutations.
ETV5	Thyroid cancer	[126]	ETV5 transactivated TERT in thyroid cancer cells lacking GABP activity.
	Thyroid cancer	[127]	MAPK pathway inhibition suppressed TERT in TPM cells and the expression and binding of ETV1, 4 & 5 to the mutant TERT promoter.

Point mutations in the TERT promoter generate novel ETS motifs in ~15–25% of tumours. Binding and transactivation at these sites by ETS family transcription factors displays a distinct pattern between tumour types.