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