BAX

Protein BAX map

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

Maps_Modules
 EMT  map  / EMT_REGULATORS  map
 Apoptosis  map  / APOPTOSIS_GENES  map
 Apoptosis  map  / CASPASES  map
 Apoptosis  map  / MITOCH_METABOLISM  map
 Apoptosis  map  / MOMP_REGULATION  map
 Survival  map  / PI3K_AKT_MTOR  map
 Survival  map  / WNT_NON_CANONICAL  map

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:20709625

BAX@Mitochondria

References
e_re439( EMT  map ):
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@Cytoplasm

References
e_re429( EMT  map ):
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
e_re430( EMT  map ):
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.
e_re434( EMT  map ):
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.
e_re439( EMT  map ):
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 outer membrane

References
a_re14( Apoptosis  map ):
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
a_re29( Apoptosis  map ):
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
a_re8( Apoptosis  map ):
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 cells
a_re1405:( Apoptosis  map ) PMID:16608847

BAX|​S163_pho|​T167_pho@Cytoplasm

References
a_re16( Apoptosis  map ):
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@Cytoplasm

References
a_re17( Apoptosis  map ):
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
a_re18( Apoptosis  map ):
BAX phosphorylated on S184 in response to nicotine displays a shortened half life
PMID:10725400
proteasome dependent degradation of BAX


Modifications:
In compartment: Cytoplasm
  1. BAX@Cytoplasm map

  2. BAX|​S184_pho@Cytoplasm map
  3. BAX|​S163_pho|​T167_pho@Cytoplasm map

In compartment: Mitochondria

  1. BAX@Mitochondria map

In compartment: Mitochondrial Matrix

  1. BAX@Mitochondrial Matrix map

In compartment: Mitochondrial outer membrane

  1. BAX|​S163_unk|​T167_unk@Mitochondrial outer membrane map

Participates in complexes:
In compartment: Cytoplasm

  1. BAX:​p53*@Cytoplasm map

In compartment: Mitochondria

  1. BAX:​BCL2@Mitochondria map

  2. BAX:​BCL2-XL*@Mitochondria map

In compartment: Mitochondrial outer membrane

  1. BAX|​S163_unk|​T167_unk:​BCL2@Mitochondrial outer membrane map

  2. BAX|​S163_unk|​T167_unk:​BCL2-XL*@Mitochondrial outer membrane map

Participates in reactions:
As Reactant or Product:

  1. rheavy strand transcript*@Mitochondrial Matrix map map rMT-TT@Mitochondrial Matrix map + rMT-ND5@Mitochondrial Matrix map + BARD1@Mitochondrial Matrix map + PYCARD@Mitochondrial Matrix map + BAX@Mitochondrial Matrix map + rMT-ND4@Mitochondrial Matrix map + rMT-ND4L@Mitochondrial Matrix map + BRCA1@Mitochondrial Matrix map + rMT-ND3@Mitochondrial Matrix map + BIRC5@Mitochondrial Matrix map + rMT-CO3@Mitochondrial Matrix map + rMT-ATP6@Mitochondrial Matrix map + rMT-ATP8@Mitochondrial Matrix map + rMT-TK@Mitochondrial Matrix map + rMT-CO2@Mitochondrial Matrix map + rMT-TD@Mitochondrial Matrix map + rMT-CO1@Mitochondrial Matrix map + rMT-TW@Mitochondrial Matrix map + rMT-ND2@Mitochondrial Matrix map + rMT-TM@Mitochondrial Matrix map + rMT-TI@Mitochondrial Matrix map + rMT-ND1@Mitochondrial Matrix map + rMT-TL1@Mitochondrial Matrix map + rMT-RNR2@Mitochondrial Matrix map + rMT-TV@Mitochondrial Matrix map + rMT-RNR1@Mitochondrial Matrix map + rMT-TF@Mitochondrial Matrix map + rMT-CYB@Mitochondrial Matrix map

  2. rBAX@Nucleus map map BAX@Cytoplasm map
  3. BAX|​S163_unk|​T167_unk@Mitochondrial outer membrane map map a_s4588
  4. BCL2-XL*@Mitochondrial outer membrane map + BAX|​S163_unk|​T167_unk@Mitochondrial outer membrane map map BAX|​S163_unk|​T167_unk:​BCL2-XL*@Mitochondrial outer membrane map
  5. BAX|​S163_pho|​T167_pho@Cytoplasm map map BAX|​S163_unk|​T167_unk@Mitochondrial outer membrane map
  6. BAX@Cytoplasm map map BAX|​S163_pho|​T167_pho@Cytoplasm map
  7. BAX@Cytoplasm map map BAX|​S184_pho@Cytoplasm map
  8. BAX|​S184_pho@Cytoplasm map map degraded
  9. BAX@Cytoplasm map + Ku70*@Cytoplasm map map a_s99
  10. BAX@Cytoplasm map + humanin*@Cytoplasm map map a_s109
  11. BAX@Cytoplasm map + 14-3-3*@Cytoplasm map map a_s118
  12. BAX@Cytoplasm map map BAX|​S163_unk|​T167_unk@Mitochondrial outer membrane map
  13. BCL2|​pho@Mitochondrial outer membrane map + BAX|​S163_unk|​T167_unk@Mitochondrial outer membrane map map BAX|​S163_unk|​T167_unk:​BCL2@Mitochondrial outer membrane map
  14. BCL2-XL*@Mitochondria map + BAX@Cytoplasm map map BAX:​BCL2-XL*@Mitochondria map
  15. BAX@Cytoplasm map + BCL2@Mitochondria map map BAX:​BCL2@Mitochondria map
  16. p53*@Mitochondria map + BAX@Cytoplasm map map BAX:​p53*@Cytoplasm map
  17. BAX:​p53*@Cytoplasm map map Apoptosis@Cytoplasm map
  18. BAX@Cytoplasm map map BAX@Mitochondria map
  19. BID_sub_TRUNC_endsub_*@Cytoplasm map + BAX@Cytoplasm map map s_s_wnc2_s54
  20. BAX@Cytoplasm map map BAX_sub_TRUNC_endsub_*@Cytoplasm map
  21. BAX@Cytoplasm map + BCL2-XL*@Cytoplasm map map BAX:​BCL2-XL*@Mitochondria map
  22. BAX:​BCL2-XL*@Mitochondria map + BAX_sub_TRUNC_endsub_*@Cytoplasm map map s_s_wnc2_s64 + BAX@Cytoplasm map

As Catalyser:

  1. Cytochrome_C*@Mitochondria map map Cytochrome_C*@Cytoplasm map

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