Pathway Map Details
Apoptosis and survival_Anti-apoptotic action of nuclear ESR1 and ESR2
Object list (links open in MetaCore):
18.104.22.168, MEK3 (MAP2K3), c-Myc, Nitric Oxide, SOD2, p38alpha (MAPK14), O(,2)('-), nNOS, Erk (MAPK1/3), Cytochrome c, Bcl-2, ESR2, H('+), ASK1 (MAP3K5), O(,2), c-Jun/c-Fos, MEK4 (MAP2K4), 22.214.171.124, c-Raf-1, H(,2)O(,2) cytoplasm, JNK1 (MAPK8), NF-kB p50/p65, Bax, Thioredoxin, (S)-citrulline, MEK1(MAP2K1), ESR1 (nuclear), 126.96.36.199, GTP, (L)-Arginine, c-Jun, Cyclic GMP cytosol, Protein kinase G1 alpha, Guanylate cyclase 1, soluble, Estradiol cytoplasm, MEK2(MAP2K2), NF-kB1 (p50)
Anti-apoptotic action of nuclear ESR1 and ESR2
17beta-estradiol exerts an anti-apoptotic effect on a wide variety of tissues that is mediated via activation of nuclear form of Estrogen receptor 1 ( ESR1 (nuclear) ) and Estrogen receptor 2 ( ESR2 ) , . Under 17beta-estradiol action, ESR1 (nuclear) induces transcription of B-cell CLL/lymphoma 2 ( Bcl-2) , ,  .
Upon activation by 17beta-estradiol, ESR2 promotes anti-apoptotic action via induction of expression of Nitric oxide synthase 1 (neuronal) ( nNOS ) and synthesis of Nitric oxide, which leads to activation of Guanylate cyclase 1, soluble, release of CGMP, and activation of Protein kinase cGMP-dependent (e.g., Protein kinase G1 alpha ) , , . Protein kinase G1 alpha activates Erk (MAPK1/3) possibly via V-raf-1 murine leukemia viral oncogene homolog 1 ( c-Raf-1 )/ Mitogen-activated protein kinase kinase 1 and 2 ( MEK1 and MEK2 ) pathway, and leads to activation of V-myc myelocytomatosis viral oncogene homolog ( c-Myc ) and Jun oncogene ( c-Jun ) transcription factors, which induce transcription of Thioredoxin ( c-Jun acts as a part of c-Jun/ V-fos FBJ murine osteosarcoma viral oncogene homolog ( c-Fos ) heterodimer) , , .
Thioredoxin binds to Nuclear factor of kappa light chain gene enhancer in B-cells 1 ( NF-kB1 (p50) ) and activates transcription of anti-apoptotic Bcl-2, which inhibits formation of mitochondrial permeability transition pore by BCL2-associated X protein ( Bax ), and Superoxide dismutase 2 mitochondrial ( SOD2 ). This leads to decrease in mitochondrial Superoxide anion production during apoptosis , , .
Moreover, reduced form of Thioredoxin binds and inhibits pro-apoptotic kinase ASK1 (MAP3K5) ,  which prevents activation of Mitogen-activated protein kinase kinase 3 ( MEK3(MAP2K3) ), Mitogen-activated protein kinase kinase 4 ( MEK4(MAP2K4) ), then Mitogen-activated protein kinase 14 ( p38alpha (MAPK14) ) and subsequently, Mitogen-activated protein kinase 8 ( JNK1(MAPK8) ) . Thus, inhibited p38alpha (MAPK14) and JNK1(MAPK8) both cannot promote inhibition of Bcl-2, so it prevents formation of mitochondrial permeability transition pore by Bax and release of Cytochrome C from mitochondria .
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