Fig. 3
From: ETS-targeted therapy: can it substitute for MEK inhibitors?
ETS1/2 interacts with CBP/p300 to transactivate target genes. ERK1/2-phosphorylated ETS1 at Thr38 and Ser41, or ETS2 at Thr72 and Ser75, which enhances an association with two closely related transcriptional co-activating proteins, CBP and p300. The binding promotes the assembly of RNA polymerase II and the basal machinery at the initiation of transcription. AKT is likely to activate the ETS1/2-containing transcription factor-enhancer complex by phosphorylating CBP or p300, histone acetyltransferases (HAT) that possess bromodomain (BRD). BRD4 is often co-localized with ETS1 and probably with ETS2 in transcription factor-enhancer complex. Thus, we may inhibit ETS1/2 activity by trametinib (MEK inhibitor), apitolisib (PI3K/mTOR inhibitor), C646 (CBP HAT inhibitor), PF-CBP1 or SGC-CBP30 (CBP BRD inhibitor), or JQ1 or OTX015 (BRD4 inhibitor)