BAX

Protein BAX

Identifiers
BCL2-associated X protein
HUGO:BAX, HGNC:959, ENTREZ:581, UNIPROT:Q07812, GENECARDS:GC19P049458
HUGO:BAX HGNC:959 ENTREZ:581 UNIPROT:Q07812
HUGO:BAX HGNC:959 ENTREZ:581 UNIPROT:Q07812 GENECARDS:BAX REACTOME:50715 KEGG:581 ATLASONC:BAXID128ch19q13 WIKI:BAX

Maps_Modules
HMC:ACTIVATING_INVASION_AND_METASTASIS
EMT Senescence / EMT_REGULATORS
EMT Senescence / MITOCHONDRIA_OXIDATIVE_STRESS
EMT Senescence / SENESCENCE
HMC:RESISTING_CELL_DEATH
HMC:DEREGULATING_CELLULAR_ENERGETICS
Regulated Cell Death / APOPTOSIS
Regulated Cell Death / STARVATION_AUTOPHAGY
Regulated Cell Death / CASPASES
Regulated Cell Death / DEATH_RECEPTOR_PATHWAYS
Regulated Cell Death / MITOCHONDRIAL_GENES
Regulated Cell Death / MITOCHONDRIAL_METABOLISM
Regulated Cell Death / MOMP_REGULATION
Regulated Cell Death / NECROPTOSIS
Regulated Cell Death / RCD_GENES
Regulated Cell Death / ER_STRESS
HMC:EVADING_GROWTH_SUPPRESSORS
Survival / PI3K_AKT_MTOR
Survival / WNT_NON_CANONICAL

References
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:8358790
Bax homodimerizes and forms heterodimers with BCL2 in vivo.
Overexpressed Bax accelerates apoptotic death induced by cytokine deprivation in an IL-3-dependent cell line.
Overexpressed Bax also counters the death repressor activity of BCL2.
These data suggest a model in which the ratio of BCL2 to Bax determines survival or death following an apoptotic stimulus.
PMID:7644501
The susceptibility to apoptosis is determined by multiple competing dimerizations in which Bax may be a common partner.
Multiple BCL2 family members demonstrate selective dimerizations with Bax
PMID:21641962
The pro-apoptototic protein Bax plays a central role in the mitochondria- dependent apoptotic pathway.
In healthy mammalian cells, Bax is essentially cytosolic and inactive.
Following a death signal, the protein is translocated to the outer mitochondrial membrane, where it promotes a permeabilization that favors the release of different apoptogenic factors, such as cytochrome c.
PMID:23064052
Inactive Bax can be directly converted into an active conformation following the interaction with activator Bid , Bim (BCL2L11) or Puma (BBC3)
The interaction of Bax with BCL2 or BCL2L1 drives the translocation of Bax to the outer mitochondrial membrane
Under this condition, active Bax can be liberated from its interaction with BCL2L1 by a derepressor BH3-only protein, such as Bad.
Other experiments have shown that Bax can be translocated to the outer mitochondrial membrane and further activated by different proteins such as Myc or p38MapK
PMID:23850759
PMID:23430059
Bax and Bak positively modulate the amplitude of IRE1asignaling by interacting at the ER with the cytoplasmic domains of IRE1a resulting in increased XBP1s and JNK phosphorylation
PMID:23377657
PMID:20709625

BAX@Cytosol

References
em_re1540( EMT Senescence ):
PMID:15613549
BAX expression was regulated by LMP-1 activation of nuclear factor kappaB
em_emtc_emtc_re429( EMT Senescence ):
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 protines) promote apoptosis, while others such as BCL2, BCL2L1, BCL2L2 (anti-apoptotic protines)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:22836101
BCL2L1 (BCL-X) promotes survival of adult and developing retinal ganglion cells.
The activation of the pro-death family member BAX is often the final step before cell death in neurons.
Pro-survival family members such as BCL2L1 act to inhibit BAX activation
em_emtc_emtc_re430( EMT Senescence ):
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.
PMID:9872359
A oncogene-derived protein, Bcl2, confers negative control in the pathway of cellular suicide machinery.
A Bcl2-homologous protein, Bax, promotes cell death by competing with Bcl2.
While Bax???Bax homodimers act as apoptosis inducers, Bcl2??? Bax heterodimer formation evokes a survival signal for the cells.
Both Bcl2 and Bax are transcriptional targets for the tumour suppressor protein, p53, which induces cell cycle arrest or apoptosis in response to DNA damage.
em_emtc_emtc_re434( EMT Senescence ):
PMID:14963330
Cytosolic localization of endogenous p53 was necessary and sufficient for apoptosis.
p53 directly activated the pro-apoptotic BCL2 protein Bax in the absence of other proteins to permeabilize mitochondria and engage the apoptotic program.
em_emtc_emtc_re439( EMT Senescence ):
PMID:17464323
Translocation of p57Kip2 to mitochondria occurs within 20 min after staurosporine (apoptotic agent) application.
In fact, p57Kip2 primarily promotes the intrinsic apoptotic pathways, favoring Bax activation and loss of mitochondrial transmembrane potential, consequent release of cytochrome-c into cytosol, caspase-9 and caspase-3 activation.
In accordance, Bcl2 overexpression is able to inhibit p57Kip2 cell death promoting effect.
Thus, in addition to its established function in control of proliferation, these results reveal a mechanism whereby p57Kip2 influences the mitochondrial apoptotic cell death pathway in cancer cells.

BAX@Mitochondria

References
em_emtc_emtc_re439( EMT Senescence ):
PMID:17464323
Translocation of p57Kip2 to mitochondria occurs within 20 min after staurosporine (apoptotic agent) application.
In fact, p57Kip2 primarily promotes the intrinsic apoptotic pathways, favoring Bax activation and loss of mitochondrial transmembrane potential, consequent release of cytochrome-c into cytosol, caspase-9 and caspase-3 activation.
In accordance, Bcl2 overexpression is able to inhibit p57Kip2 cell death promoting effect.
Thus, in addition to its established function in control of proliferation, these results reveal a mechanism whereby p57Kip2 influences the mitochondrial apoptotic cell death pathway in cancer cells.

BAX|S163_unk|T167_unk@Mitochondrial inner membrane

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 / DEATH_RECEPTOR_PATHWAYS
Regulated Cell Death / MITOCHONDRIAL_GENES
Regulated Cell Death / MITOCHONDRIAL_METABOLISM
Regulated Cell Death / MOMP_REGULATION
Regulated Cell Death / NECROPTOSIS
Regulated Cell Death / RCD_GENES

References
rc_re14( Regulated Cell Death ):
PMID:15486085
in FL5.12 cells correlation of BIM-BAX interaction in mitochondrial fractions with presence of unphosphorylated S65 BimEL
non phosphorylatable BimEL: enhanced interaction with BAX and enhanced proapoptotic activity
PMID:12419244
in vitro in reconstituted vesicles, BID induces BAX and membrane permeabilization
rc_re29( Regulated Cell Death ):
PMID:19968986
cleaved MCL1
PMID:14730312
ASC/PYCARD
PMID:19062087
in vitro in reconstituted liposomes, tBid is sufficient to induce Bax insertion into membrane and oligomerization
rc_re8( Regulated Cell Death ):
in Ba/F3 cells, stable expression of the C-terminal cleavage product of BECN1 sensitizes cells to IL3-deprivation induced apoptosis
in vitro, incubation of isolated mitochondria with recombinant BECN1 C-terminal cleavage product triggers release of Omi/HtrA2 and cytochrome c
PMID:11832478
in vitro CASP2 unlike CASP8 induce release of CYCS , DIABLO and AIF form purified mitochondria from Hela cellsPMID: PMID:23242420
calpain-mediated Bax and Atg5 cleavage resulted in the collapse of the mitochondrial membrane potential and cytochrome c release
rc_re1405:( Regulated Cell Death ) PMID:16608847
rc_re1840( Regulated Cell Death ):
PMID:23242420
Calcium induced calpain-mediated Bax and Atg5 cleavage resulted in the collapse of the mitochondrial membrane potential and cytochrome c release

BAX|S163_pho|T167_pho@Cytosol

References
rc_re16( Regulated Cell Death ):
PMID:15525785 GSK3B mediated phosphorylation of Bax S163
in HEK293 human cells
in rat cerebellar granule neurons
PMID:16709574 JNK- and p38- dependent phosphrylation of BAX, most probably on T167
in HepG2 human hepatoma cell line
in LLC-PK1 porcine kidney cell line

BAX|S184_pho@Cytosol

References
rc_re17( Regulated Cell Death ):
The impact of the S284 phosphorylation status on the other reactions (phosphorylations, membrane insertion...) was not assessed.
PMID:14766748
Akt-dependent phosphorylation of BAX S184 upon GM-CSF
in PLB-985 human, peripheral blood, leukemia, acute myeloid
in mouse peritoneal neutrophils
PMID:15642728
Akt directly phosphorylates BAX S184 in response to nicotine
in A549 human lung cancer cell line
PMID:17525161
PRKCZ dependent phosphorylation of Bax at S184
in A549 carcinomic human alveolar basal epithelial cells exposed to nicotine
rc_re18( Regulated Cell Death ):
BAX phosphorylated on S184 in response to nicotine displays a shortened half life
PMID:10725400
proteasome dependent degradation of BAX

BAX@Mitochondrial Matrix

BAX@Lysosome

BAX|S163_unk|T167_unk@Cytosol

References
rc_re1810:( Regulated Cell Death ) PMID:16227588
rc_re1811( Regulated Cell Death ):
PMID:16227588
PMID:17891140

BAX@Endopasmic Reticulum

BAX@Cytoplasm

References
s_wnc2_re22( Survival ):
PMID:14681224, PMID:14612448
However, the mechanism in which truncated Bax increases apoptosis remains controversial.
PMID:20008353
s_wnc2_re14:( Survival ) PMID:20008353, PMID:20709625, PMID:21738214
s_wnc2_re18:( Survival ) PMID:20709625, PMID:14612448, PMID:21414921
s_wnc2_re19:( Survival ) PMID:21486225

Modifications:
In compartment: Cytoplasm

BAX@Cytoplasm

In compartment: Cytosol

BAX@Cytosol
BAX|S184_pho@Cytosol
BAX|S163_pho|active@Cytosol
BAX|S163_pho|T167_pho@Cytosol
BAX|S163_unk|T167_unk@Cytosol

In compartment: Endopasmic Reticulum

BAX@Endopasmic Reticulum

In compartment: Lysosome

BAX@Lysosome

In compartment: Mitochondria

BAX@Mitochondria

In compartment: Mitochondrial Matrix

BAX@Mitochondrial Matrix

In compartment: Mitochondrial inner membrane

BAX|S163_unk|T167_unk@Mitochondrial inner membrane

Participates in complexes:
In compartment: Cytosol

In compartment: Endopasmic Reticulum

In compartment: Mitochondria

In compartment: Mitochondrial inner membrane

Participates in reactions:
As Reactant or Product:

As Catalyser: