BCL2

Protein BCL2 map

Identifiers
B-cell CLL/lymphoma 2
HUGO:BCL2 HGNC:990 ENTREZ:596 UNIPROT:P10415 GENECARDS:BCL2 REACTOME:50758 KEGG:596 ATLASONC:BCL2ID49 WIKI:BCL2

Maps_Modules
 EMT  map  / EMT_REGULATORS  map
 Apoptosis  map  / AKT_MTOR  map
 Apoptosis  map  / APOPTOSIS_GENES  map
 Apoptosis  map  / CASPASES  map
 Apoptosis  map  / MITOCH_METABOLISM  map
 Apoptosis  map  / MOMP_REGULATION  map
 Survival  map  / MAPK  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:23064052
BCL2 and BCL2L1 are known to be overexpressed in several cancers.
BCL2 protein can target Raf-1 (C-Raf) to mitochondria.
PMID:8929532

BCL2@Mitochondria

References
e_re430( 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 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: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_re431( EMT  map ):
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.
e_re433( EMT  map ):
PMID:12667443
p53 induces apoptosis by target gene regulation and transcription-independent signaling.
A fraction of induced p53 translocates to the mitochondria of apoptosing tumor cells. Targeting p53 to mitochondria is sufficient to launch apoptosis.
Evidence that p53 translocation to the mitochondria occurs in vivo in irradiatedthymocytes was shown.
e_re436( EMT  map ):
PMID:11463392
BBC3 (so-called PUMA, p53 upregulated modulator of apoptosis) as a target for activation by p53.
This gene encodes two BH3 domain–containing proteins that are induced in cells following p53 activation.
BBC3 binds to BCL2, localize to the mitochondria to induce cytochrome c release, and activate the rapid induction of programmed cell death.
Antisense inhibition of PUMA expression reduced the apoptotic response to p53, and PUMA is likely to play a role inmediating p53-induced cell death through the cytochrome c/Apaf-1–dependent pathway.
PMID:11463391
PUMA was found to be exclusively mitochondrial and to bind to BCL2 and BCL2L1 through a BH3 domain.
It is via this binding to BBC3 (an apoptic inducer) that BCL2 and BCL2L1 exhibit their anti-apoptic effect.

BCL2|​pho@Mitochondrial outer membrane

References
a_re1409( Apoptosis  map ):
PMID:9115213
S70 phosphorylation of BCL2 necessary for its antiapoptotic function
in NSF/N1.H7 mouse leukemia cells BCL2 mutants transfection) in response to IL-3, etoposide, or bryostatin-1, a PKC activator
PMID:9738012
suggest that PRKCA is the main PRKC BCL2 kinase in HL60 human acute myeloid leukemia cell line
PMID:10677502
ERK1/2 is a BCL2 S70 kinase in NSF/N1.H7 cells stimulated with IL-3
in vitro direct phosphorylation
PMID:11323415
JNK is a BCL2 S70 kinase in NSF/N1.H7 cells upon IL-3 withdrawal
a_re102:( Apoptosis  map ) PMID:14747474
a_re582( Apoptosis  map ):
PMID:9430630
PMID:15486085
BCL2-BimEL interaction in mitochondrial fraction independent of BIM S69 phosphorylation status
PMID:15724238
in human tonsil B cells, constitutive interaction
PMID:10198631
a_re597:( Apoptosis  map ) testtest
a_re602( Apoptosis  map ):
PMID:11546872
in HEK293T, coIP
Y2H
a_re607:( Apoptosis  map ) PMID:9130713
a_re1116( Apoptosis  map ):
PMID:19834492
in different cancer cell lines (CEM, C666-1 and HCT116) that express empty or BCL2 plasmids
a_re1408:( Apoptosis  map ) reactionType:is.a

BCL2@Cytoplasm

References
a_re1387:( Apoptosis  map ) reactionType:is.a
a_re410( Apoptosis  map ):
PMID:9765397
PMID:10604474
PMID:16179260

BCL2@Mitochondrial outer membrane

References
a_re1420( Apoptosis  map ):
PMID:8929532
in vitro RAF1:BCL2 interaction
in 293, overexpression of BCL2 induces relocalization of RAF1-GFP to mitochondria
in vitro phosphorylation of BAD by RAF1
in 293T, over-expression of a mitochondria-targeted version of RAF1 induces phosphorylation of BAD (controls: plasma membrane targeted RAF1, kinase dead mutant)
BCL2 over-expression targets RAF1 kinase domain-GFP to mitochondria
mitochondria-targeted RAF1 (deleted for Ras binding domain) potentiates BCL2 anti-apoptotic activity in 32D.3 exposed to staurosporine or upon IL-3 withdrawal
a_re1407:( Apoptosis  map ) reactionType:is.a
a_re1409( Apoptosis  map ):
PMID:9115213
S70 phosphorylation of BCL2 necessary for its antiapoptotic function
in NSF/N1.H7 mouse leukemia cells BCL2 mutants transfection) in response to IL-3, etoposide, or bryostatin-1, a PKC activator
PMID:9738012
suggest that PRKCA is the main PRKC BCL2 kinase in HL60 human acute myeloid leukemia cell line
PMID:10677502
ERK1/2 is a BCL2 S70 kinase in NSF/N1.H7 cells stimulated with IL-3
in vitro direct phosphorylation
PMID:11323415
JNK is a BCL2 S70 kinase in NSF/N1.H7 cells upon IL-3 withdrawal

BCL2|​unk@Mitochondrial outer membrane

References
a_re1407:( Apoptosis  map ) reactionType:is.a
a_re1000( Apoptosis  map ):
influenceDelete: reactants to re
hierarchical:post-MOMP
reactionType:casp.cleavage
PMID:10409669
CASP3 mediated cleavage of BCL2 in vitro and in HL60 cells or MCF7 with reconstituted CASP3 expression after exposure to staurosporine
no cleavage by CASP7
PMID:20139069
FKBP8 protects BCL2 from CASP3-mediated degradation
a_re1001( Apoptosis  map ):
PMID:19706769
in HEK293, co-precipitation of ectopically expressed tagged proteins
in HeLa cells infected with G0S2-HA Ad virus, co-precipitation of endogenous BCL2 with HA antibody
in HCT116 (transient transfection), interaction detected by FRET
Competition between G0S2 and BAX for binding to BCL2
in HEK293, co-IP experiments with tagged protein shows that G0S2 competes with BAX for binding to BCL2
a_re1002:( Apoptosis  map ) PMID:9660918
a_re1406( Apoptosis  map ):
PMID:18845789
unphosphorylated TP53 from coIP experiments with okadaic acid (PKC inhibitor) or ceramide C2 (potent inductor of PP1/2A
a_re1410( Apoptosis  map ):
PMID:14980220
in vitro with in vitro translated proteins
in H460 cells (endogenously expressed proteins), upon 3-Cl-AHPC
effect of Bcl2 phosphorylation on binding to NUR77 unknown, even if loop region of Bcl2 between BH3 and BH4, which contains the phosphorylation sites, domain was mapped as the interaction domain

BCL2|​ubi@Cytoplasm

References
a_re1469:( Apoptosis  map ) PMID:20865015


Modifications:
In compartment: Cytoplasm
  1. BCL2@Cytoplasm map

  2. BCL2|​ubi@Cytoplasm map

In compartment: Mitochondria

  1. BCL2@Mitochondria map

In compartment: Mitochondrial outer membrane

  1. BCL2@Mitochondrial outer membrane map

  2. BCL2|​pho@Mitochondrial outer membrane map
  3. BCL2|​unk@Mitochondrial outer membrane map

Participates in complexes:
In compartment: Cytoplasm

  1. BCL2:​BECN1@Cytoplasm map

In compartment: Mitochondria

  1. BAX:​BCL2@Mitochondria map

  2. BAK1:​BCL2@Mitochondria map
  3. BBC3:​BCL2@Mitochondria map
  4. BCL2:​p53*@Mitochondria map

In compartment: Mitochondrial outer membrane

  1. BCL2:​HRK@Mitochondrial outer membrane map

  2. BBC3:​BCL2@Mitochondrial outer membrane map
  3. BCL2:​G0S2@Mitochondrial outer membrane map
  4. BCL2:​p53*@Mitochondrial outer membrane map
  5. BCL2:​TMBIM6@Mitochondrial outer membrane map
  6. BCL2:​BCL2L11@Mitochondrial outer membrane map
  7. BCL2:​BMF|​unk@Mitochondrial outer membrane map
  8. BCL2|​unk:​NR4A1@Mitochondrial outer membrane map
  9. BAD|​S91_unk:​BCL2@Mitochondrial outer membrane map
  10. BCL2:​cleaved_BID*|​myr@Mitochondrial outer membrane map
  11. BAX|​S163_unk|​T167_unk:​BCL2@Mitochondrial outer membrane map

Participates in reactions:
As Reactant or Product:

  1. BCL2|​unk@Mitochondrial outer membrane map map cleaved~BCL2*@Mitochondrial outer membrane map

  2. BCL2|​unk@Mitochondrial outer membrane map + G0S2@Cytoplasm map map BCL2:​G0S2@Mitochondrial outer membrane map
  3. TMBIM6@Mitochondrial outer membrane map + BCL2|​unk@Mitochondrial outer membrane map map BCL2:​TMBIM6@Mitochondrial outer membrane map
  4. rBCL2@Nucleus map map BCL2@Cytoplasm map
  5. BCL2@Cytoplasm map map BCL2|​unk@Mitochondrial outer membrane map
  6. BCL2@Cytoplasm map map BCL2@Cytoplasm map
  7. BCL2|​unk@Mitochondrial outer membrane map + p53*|​S15_unk@Cytoplasm map map BCL2:​p53*@Mitochondrial outer membrane map
  8. BCL2@Mitochondrial outer membrane map map BCL2|​unk@Mitochondrial outer membrane map
  9. BCL2|​pho@Mitochondrial outer membrane map map BCL2|​unk@Mitochondrial outer membrane map
  10. BCL2@Mitochondrial outer membrane map map BCL2|​pho@Mitochondrial outer membrane map
  11. BCL2|​unk@Mitochondrial outer membrane map + NR4A1@Cytoplasm map map BCL2|​unk:​NR4A1@Mitochondrial outer membrane map
  12. BAD|​S91_unk:​BCL2@Mitochondrial outer membrane map map BCL2@Mitochondrial outer membrane map + BAD|​pho@Cytoplasm map
  13. BCL2@Cytoplasm map map BCL2|​ubi@Cytoplasm map
  14. BCL2|​ubi@Cytoplasm map map degraded
  15. BECN1@Cytoplasm map + BCL2@Cytoplasm map map BCL2:​BECN1@Cytoplasm map
  16. BCL2L11@Mitochondrial outer membrane map + BCL2|​pho@Mitochondrial outer membrane map map BCL2:​BCL2L11@Mitochondrial outer membrane map
  17. cleaved_BID*|​myr@Mitochondrial outer membrane map + BCL2|​pho@Mitochondrial outer membrane map map BCL2:​cleaved_BID*|​myr@Mitochondrial outer membrane map
  18. BBC3@Mitochondrial outer membrane map + BCL2|​pho@Mitochondrial outer membrane map map BBC3:​BCL2@Mitochondrial outer membrane map
  19. BAD|​S91_unk|​active@Cytoplasm map + BCL2|​pho@Mitochondrial outer membrane map map BAD|​S91_unk:​BCL2@Mitochondrial outer membrane map
  20. BMF|​unk@Mitochondrial outer membrane map + BCL2|​pho@Mitochondrial outer membrane map map BCL2:​BMF|​unk@Mitochondrial outer membrane map
  21. HRK@Mitochondrial outer membrane map + BCL2|​pho@Mitochondrial outer membrane map map BCL2:​HRK@Mitochondrial outer membrane map
  22. 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
  23. BAD_binding partners*@Mitochondria map map BCL2@Mitochondria map
  24. BAX@Cytoplasm map + BCL2@Mitochondria map map BAX:​BCL2@Mitochondria map
  25. BCL2@Mitochondria map + BAK1@Mitochondria map map BAK1:​BCL2@Mitochondria map
  26. p53*@Mitochondria map + BCL2@Mitochondria map map BCL2:​p53*@Mitochondria map
  27. BBC3@Mitochondria map + BCL2@Mitochondria map map BBC3:​BCL2@Mitochondria map
  28. gBCL2@Nucleus map map BCL2@Mitochondria map
  29. s_s_mpk1_s953 map BCL2@Mitochondria map + BAD@Mitochondria map

As Catalyser:

  1. cleaved~Caspase9*@Mitochondrial intermembrane space map map cleaved~Caspase9*@Cytoplasm map

  2. COX5A@Cytoplasm map map COX5A@Mitochondrial inner membrane map
  3. GRB2:​RAF1|​pho:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map map GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map + RAF1|​pho@Mitochondria map

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