MetforminMetformin-activated AMPK(Thr172) phosphorylates p53(Ser15) indirectly via ATM/CHK2 axisp53(Ser15)-phosphorylated transactivates PUMA(BBC3) promoter via p53 response elementsPUMA(BH3 domain) protein elevatedbinds BCL-2(BH3 groove) and BCL-XL(BH3 groove) displacing BAXBAX released → BAX(Ser184)-dephosphorylated inserts into OMMMetformin-induced ROS activates ATF3/ATF4 via eIF2α(Ser51) phosphorylation (ISR pathway)ATF4 transactivates NOXA(PMAIP1) promoterNOXA(BH3 domain) selectively binds MCL-1(BH3 groove) and BCL2A1 displacing BAKBAK oligomerises at OMM forming cytochrome c-releasing porescytochrome c binds APAF1 → apoptosome → caspase-9(Asp315) cleavagecaspase-3(Asp175) cleavedCancer Score: 0.9012 hops
Pathway Hops
PHOSPHORYLATESConfidence: 95%
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