Our present study brought insights into the mechanism underlying this synergistic oncogenic operation of BRAF V600E and TERT promoter mutations by demonstrating a robust cooperative role of the two mutations in the expression of TERT, through the BRAF V600E → MAPK pathway → FOS → GABP → TERT axis. Using thyroid cancer and melanoma cells as cancer cell models that harbored BRAF V600E and TERT promoter mutations, we demonstrated that the BRAF V600E/MAPK pathway promoted the formation and binding of transcriptional GABP complex to the mutated TERT promoter and its activation. Specifically, we identified GABPB, the catalytic unit of the GABP complex, but not the DNA binding unit GABPA, as a downstream target gene of the BRAF V600E/MAPK pathway; BRAF V600E-activated MAP kinase pathway strongly upregulated the transcriptional expression of GABPB, thus driving the production of GABP complex, which in turn robustly promoted the expression of TERT. This represents a major progress in understanding the transcriptional machinery of the mutant TERT promoter involving GABP described recently31,32 by adding a critical regulatory dimension to it.