Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.11.24 (
mitogen-activated protein kinase
)
95,810
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The unique oncogene duet of coexisting BRAF V600E and TERT promoter mutations are widely found to be a robust genetic background promoting human cancer aggressiveness, but the mechanism is unclear. Here, we demonstrate that the BRAF V600E/
MAP kinase
pathway phosphorylates and activates FOS, which in turn acts as a transcription factor to bind and activate the
GABPB
promoter, increasing
GABPB
expression and driving formation of GABPA-
GABPB
complex; the latter selectively binds and activates mutant TERT promoter, upregulating TERT expression. Elevated TERT functions as a strong oncoprotein, robustly promoting aggressive behaviors of cancer cells and tumor development. We thus identify a molecular mechanism for the activation of mutant TERT by the BRAF V600E/
MAP kinase
pathway, in which FOS as a transcriptional factor of
GABPB
promoter plays a key role in functionally bridging the two oncogenes in cooperatively promoting oncogenesis, providing important cancer biological and clinical implications.
...
PMID:Regulation of mutant TERT by BRAF V600E/MAP kinase pathway through FOS/GABP in human cancer. 2942 27
