Identifiers
HGNC:936
HUGO:BAD
BCL2-associated agonist of cell death
HUGO:BAD, HGNC:936, ENTREZ:572, UNIPROT:Q92934, GENECARDS:GC11M064037
HUGO:BAD HGNC:936 ENTREZ:572 UNIPROT:Q92934
HUGO:BAD HGNC:936 ENTREZ:572 UNIPROT:Q92934 GENECARDS:BAD REACTOME:50663 KEGG:572 ATLASONC:BADID130ch11q13 WIKI:BAD
Maps_Modules
HMC:AVOIDING_IMMUNE_DESTRUCTION
Adaptive Immune Response / TCR_SIGNALING
HMC:ACTIVATING_INVASION_AND_METASTASIS
EMT Senescence / EMT_REGULATORS
EMT Senescence / MITOCHONDRIA_OXIDATIVE_STRESS
HMC:RESISTING_CELL_DEATH
HMC:DEREGULATING_CELLULAR_ENERGETICS
Regulated Cell Death / APOPTOSIS
Regulated Cell Death / STARVATION_AUTOPHAGY
Regulated Cell Death / CASPASES
Regulated Cell Death / GLUCOSE_METABOLISM
Regulated Cell Death / MITOCHONDRIAL_METABOLISM
Regulated Cell Death / MOMP_REGULATION
Regulated Cell Death / NECROPTOSIS
HMC:EVADING_GROWTH_SUPPRESSORS
Survival / MAPK
Survival / PI3K_AKT_MTOR
Survival / WNT_NON_CANONICAL
References
PMID:9346240
PMID:11342610
PMID:22039431
The Bcl2 family proteins regulate and mediate the mitochondrial outer membrane permeabilization, a crucial event in the mitochondrial pathway of apoptosis in vertebrates.
The regulation of apoptosis is governed largely by interactions between the pro-survival and pro-death members of the Bcl2 protein family.
Some members of this family (e.g., Bax, Bak, and Bid: pro-apoptotic proteins) promote apoptosis, while others such as BCL2, BCL2L1, BCL2L2 (anti-apoptotic proteins) work against programmed cell death.
The BCL2 family proteins are characterized by regions of specific sequence homology named as BCL2 homology (BH) motifs that number from 1 to 4 and are critical for function.
Especially a helical BH3 motif of pro-apoptotic proteins occupy and form strong interactions with hydrophobic groove of anti-apoptotic BCL2 family proteins which leads to the activation of the essential death mediators Bax and Bak, thereby committing cells to apoptosis
PMID:12175651
PMID:10826997
PMID:12767520
PMID:19030972
PMID:16931767
PMID:21540285
PMID:12444011
IGFfamily exhibits anti-apoptotic activity.
Three IGF1R-induced anti-apoptotic pathways:
1. IRS1-mediated pathway causing activation of PI3K and AKT(PKB) leading to BAD phosphorylation.
Unphosphorylated BAD, by binding to BCLXL and BCL2, neutralizes the protective effect of these 2 later proteins and promotes cell death.
Phosphorylated BAD is sequestered by 14-3-3 protein family and thus unable to bind BCL2 family hence can not promote cell death.
2. After autophosphorylation and thus activation, IGF1R binds to 14-3-3 protein family, leading to activation and translocation of c-Raf1 to the mitochondria where it phosphorylates BAD.
3. IGF1R specifically phosphorylates and inhibits ASK1 (MAP3K5)
IRS3 and IRS4 however have negative effect on anti-apoptotic effects of IGFR.
there are at least 2 isoforms of BAD. Here, protein BAD refers to any of the different isoforms. Numbering of amino-acids, used for phosphorylation sites, are adjusted to the 'canonical' isoform as defined in Uniprot. This lead to choosing different isoforms for different organisms.
A mitochondrial pool of Raf-1 (C-RAF) molecules which do not activate MEK reportedly exert their prosurvival effects upstream of cytochrome c release by phosphorylating the pro-apoptotic Bcl-2 family member BAD. Phosphorylation of BAD results in its translocation to the cytosol and ultimately in the inhibition of cytochrome c release.
PMID:12107820
PMID:10949026
PMID:19641503
References
an_re33:( Angiogenesis ) PMID:9346240
References
an_re33:( Angiogenesis ) PMID:9346240
References
em_emtc_emtc_re1610( EMT Senescence ):
PMID:12175651
PMID:10826997
PMID:12767520
PMID:19030972
PMID:16931767
PMID:21540285
PMID:12444011
IGFfamily exhibits anti-apoptotic activity.
Three IGF1R-induced anti-apoptotic pathways:
1. IRS1-mediated pathway causing activation of PI3K and AKT(PKB) leading to BAD phosphorylation.
Unphosphorylated BAD, by binding to BCLXL and BCL2, neutralizes the protective effect of these 2 later proteins and promotes cell death.
Phosphorylated BAD is sequestered by 14-3-3 protein family and thus unable to bind BCL2 family hence can not promote cell death.
2. After autophosphorylation and thus activation, IGF1R binds to 14-3-3 protein family, leading to activation and translocation of c-Raf1 to the mitochondria where it phosphorylates BAD.
3. IGF1R specifically phosphorylates and inhibits ASK1 (MAP3K5)
References
em_emtc_emtc_re1610( EMT Senescence ):
PMID:12175651
PMID:10826997
PMID:12767520
PMID:19030972
PMID:16931767
PMID:21540285
PMID:12444011
IGFfamily exhibits anti-apoptotic activity.
Three IGF1R-induced anti-apoptotic pathways:
1. IRS1-mediated pathway causing activation of PI3K and AKT(PKB) leading to BAD phosphorylation.
Unphosphorylated BAD, by binding to BCLXL and BCL2, neutralizes the protective effect of these 2 later proteins and promotes cell death.
Phosphorylated BAD is sequestered by 14-3-3 protein family and thus unable to bind BCL2 family hence can not promote cell death.
2. After autophosphorylation and thus activation, IGF1R binds to 14-3-3 protein family, leading to activation and translocation of c-Raf1 to the mitochondria where it phosphorylates BAD.
3. IGF1R specifically phosphorylates and inhibits ASK1 (MAP3K5)
Maps_Modules
HMC:RESISTING_CELL_DEATH
HMC:DEREGULATING_CELLULAR_ENERGETICS
Regulated Cell Death / APOPTOSIS
Regulated Cell Death / STARVATION_AUTOPHAGY
Regulated Cell Death / CASPASES
Regulated Cell Death / GLUCOSE_METABOLISM
Regulated Cell Death / MITOCHONDRIAL_METABOLISM
Regulated Cell Death / MOMP_REGULATION
Regulated Cell Death / NECROPTOSIS
References
rc_re638( Regulated Cell Death ):
reactionType:is.a
logical:re631_s3146_re638=FALSE
logical:re633_s3146_re638=FALSE
rc_re630( Regulated Cell Death ):
PMID:12049737
in vitro with recombinant murine proteines
in COS cells with ectopic expression of BAD
in rat granule neurons upon suppression of neuronal activity, cdc2 is induced, phosphorylates BAD S128
in rat neurones expressing ectopic proteins, cdc2 induced apoptosis is inhibited by a BAD S118 mutant
in vitro, AKT mediated BAD S136 phosphorylation is not blocked by prior cdc2 mediated BAD S128 phosphorylations
BAD S128 phosphorylation inhibits BAD phospho S136 : 14-3-3 interaction
rc_re1242( Regulated Cell Death ):
PMID:11287608
in 32D murine cells, upon IL3 withdrawal, BAD cleavage
in vitro cleavage of BAD by recombinant CASP 2,3,7,8,10, and GZMB
Maps_Modules
HMC:RESISTING_CELL_DEATH
HMC:DEREGULATING_CELLULAR_ENERGETICS
Regulated Cell Death / APOPTOSIS
Regulated Cell Death / STARVATION_AUTOPHAGY
Regulated Cell Death / CASPASES
Regulated Cell Death / GLUCOSE_METABOLISM
Regulated Cell Death / MITOCHONDRIAL_METABOLISM
Regulated Cell Death / MOMP_REGULATION
Regulated Cell Death / NECROPTOSIS
References
rc_re1244:( Regulated Cell Death ) reactionType:is.a
rc_re641( Regulated Cell Death ):
PMID:12931191
in mouse liver mitochondria, protein complex purification
Maps_Modules
HMC:RESISTING_CELL_DEATH
HMC:DEREGULATING_CELLULAR_ENERGETICS
Regulated Cell Death / APOPTOSIS
Regulated Cell Death / STARVATION_AUTOPHAGY
Regulated Cell Death / CASPASES
Regulated Cell Death / GLUCOSE_METABOLISM
Regulated Cell Death / MITOCHONDRIAL_METABOLISM
Regulated Cell Death / MOMP_REGULATION
Regulated Cell Death / NECROPTOSIS
References
rc_re630( Regulated Cell Death ):
PMID:12049737
in vitro with recombinant murine proteines
in COS cells with ectopic expression of BAD
in rat granule neurons upon suppression of neuronal activity, cdc2 is induced, phosphorylates BAD S128
in rat neurones expressing ectopic proteins, cdc2 induced apoptosis is inhibited by a BAD S118 mutant
in vitro, AKT mediated BAD S136 phosphorylation is not blocked by prior cdc2 mediated BAD S128 phosphorylations
BAD S128 phosphorylation inhibits BAD phospho S136 : 14-3-3 interaction
rc_re1244:( Regulated Cell Death ) reactionType:is.a
Maps_Modules
HMC:RESISTING_CELL_DEATH
HMC:DEREGULATING_CELLULAR_ENERGETICS
Regulated Cell Death / APOPTOSIS
Regulated Cell Death / STARVATION_AUTOPHAGY
Regulated Cell Death / CASPASES
Regulated Cell Death / GLUCOSE_METABOLISM
Regulated Cell Death / MITOCHONDRIAL_METABOLISM
Regulated Cell Death / MOMP_REGULATION
Regulated Cell Death / NECROPTOSIS
References
rc_re597:( Regulated Cell Death ) testtest
References
su_mpk1_mpk1_re118( Survival ):
A mitochondrial pool of Raf-1 (C-RAF) molecules which do not activate MEK reportedly exert their prosurvival effects upstream of cytochrome c release by phosphorylating the pro-apoptotic Bcl-2 family member BAD. Phosphorylation of BAD results in its translocation to the cytosol and ultimately in the inhibition of cytochrome c release.
PMID:12107820
References
s_wnc2_re30:( Survival ) PMID:22088220
References
s_wnc2_re31:( Survival ) PMID:22088220
→ BAD|pho@T_cell
→ Regulation_of_T-cell_apoptosis@T_cell
→ Apoptosis@Cytosol
→ BAD|pho@Cytosol
→ BAD|pho@Mitochondria
+ BAD@Mitochondria → BAD:BAD_binding partners*@Mitochondria
→ Apoptosis@Cytosol
+ 14-3-3*@Cytosol → 14-3-3*:BAD|pho@Cytosol
→ cleaved~BAD*@Cytosol
→ BAD|unk@Cytosol
→ BAD|S91_unk|active@Cytosol
→ BAD|S91_unk|active@Cytosol
→ BCL2@Mitochondrial inner membrane + BAD|pho@Cytosol
+ BAD|S91_unk|active@Cytosol → BAD|S91_unk|active:BCL2-XL*@Cytosol
→ BAD|S91_unk|active@Mitochondrial inner membrane
+ BCL2|pho@Mitochondrial inner membrane → BAD|S91_unk:BCL2@Mitochondrial inner membrane
+ BCL2-XL*@Mitochondrial inner membrane → BAD|S91_unk:BCL2-XL*@Mitochondrial inner membrane
+ BCL2L2@Mitochondrial inner membrane → BAD|S91_unk:BCL2L2@Mitochondrial inner membrane
→ BAD|S91_pho|unk@Cytosol
→ BAD|pho@Cytosol
+ 14-3-3*|unk@Cytosol → rc_s3150
→ BAD@Cytosol
→ BAD|unk@Cytosol
+ GCK@Cytosol + WASF1@Cytosol + PRKAC*@Cytosol + PPP1C*@Cytosol → BAD|S91_unk:GCK:PPP1C*:PRKAC*:WASF1@Mitochondrial inner membrane
→ BAD|S91_unk|pho:GCK:PPP1C*:PRKAC*:WASF1@Mitochondrial inner membrane
→ BAD|S91_unk:GCK:PPP1C*:PRKAC*:WASF1@Mitochondrial inner membrane
→ 14-3-3*:BAD|S112_pho|S136_pho@Mitochondria
→ 14-3-3*:BAD|S112_pho|S136_pho|S155_pho@Mitochondria
→ 14-3-3*:BAD|S112_pho|S136_pho|S155_pho@Mitochondria + BCL2-XL*@Mitochondria
→ 14-3-3*:BAD|S112_pho|S136_pho|S155_pho@Cytoplasm
→ BAD|pho@Cytoplasm
→ Apoptosis@Cytoplasm
BCL2@Mitochondria + BAD@Mitochondria
→ 14-3-3*:BAD|pho|pho@Cytoplasm
→ Survival@Mitochondria
→ MOMP@Mitochondria
→ 14-3-3*:BAD|pho|pho|pho@Cytoplasm
→ BAD|pho|pho@Cytoplasm + 14-3-3*@Cytoplasm
→ BAD|pho|pho@Mitochondria
→ 14-3-3*:BAD|pho|pho|pho@Mitochondria