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Biological Pathway
Cite
Metformin
Metformin-activated AMPK(Thr172) phosphorylates p53(Ser15) indirectly via ATM/CHK2 axis
p53(Ser15)-phosphorylated transactivates PUMA(BBC3) promoter via p53 response elements
PUMA(BH3 domain) protein elevated
binds BCL-2(BH3 groove) and BCL-XL(BH3 groove) displacing BAX
BAX released → BAX(Ser184)-dephosphorylated inserts into OMM
Metformin-induced ROS activates ATF3/ATF4 via eIF2α(Ser51) phosphorylation (ISR pathway)
ATF4 transactivates NOXA(PMAIP1) promoter
NOXA(BH3 domain) selectively binds MCL-1(BH3 groove) and BCL2A1 displacing BAK
BAK oligomerises at OMM forming cytochrome c-releasing pores
cytochrome c binds APAF1 → apoptosome → caspase-9(Asp315) cleavage
caspase-3(Asp175) cleaved
Cancer
Score: 0.90
12 hops
Pathway Hops
PHOSPHORYLATES
Confidence: 95%
ACTIVATES
Confidence: 95%
PROMOTES
Confidence: 95%
INHIBITS
Confidence: 95%
CAUSES
Confidence: 95%
CAUSES
Confidence: 95%
ACTIVATES
Confidence: 95%
INDUCES
Confidence: 95%
CAUSES
Confidence: 95%
ACTIVATES
Confidence: 95%
ACTIVATES
Confidence: 95%
PROMOTES
Confidence: 95%
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Metformin → Cancer — Biological Pathway | InTree.AI | InTree