Relation Results

Summary

Name BCL2
Full Name Apoptosis regulator Bcl-2
Synonyms BCL2_HUMAN
Primary ID P10415
Links - -
Type protein
Relations 83
Pathways Alzheimer, Acute Myeloid Leukemia, BCR-ABL in AML, DNMT3A in AML, FLT3 in AML, KIT in AML, miRNA in AML, MLL fusion protein in AML, AML_TRIPLETS, Autophagy, COVID-19 Causal Network, Colorectal Carcinoma, Death Receptor Signaling, FLT3-ITD signaling, GLP-1 and GIP receptor signaling in PDAC, Inhibition of Apoptosis, Mitochondrial Control of Apoptosis, Malignant Melanoma, Triple mutant AML, NPM1_new, Non-small-cell lung cancer (NSCLC), p53 in cancer, SARS-COV APOPTOSIS, SARS-CoV MAPK PERTURBATION
Inhibitors gossypol; Obatoclax mesylate; ABT-737; 4-[4-[[2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohexenyl]methyl]-1-piperazinyl]-N-[4-[[(2R)-4-(4-morpholinyl)-1-(phenylthio)butan-2-yl]amino]-3-(trifluoromethylsulfonyl)phenyl]sulfonylbenzamide; venetoclax; N-[4-(2-tert-butylphenyl)sulfonylphenyl]-2,3,4-trihydroxy-5-[(2-propan-2-ylphenyl)methyl]benzamide; Obatoclax
Function Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling ...
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Type: Score: Layout: SPV 
0.5710.5480.20.20.3120.540.3530.20.3750.4620.3370.3490.6260.80.70.80.480.20.4620.20.20.8140.6680.6540.4210.7960.80.80.7340.2510.4950.6360.2650.3890.20.20.20.20.70.7430.20.6260.20.20.2530.20.4470.80.4790.20.20.20.80.20.8MAPK8BCL2MAPK3ERK1/2JNKPPP2R5BMAPK1PRKCAp38PPP2CBPPP2CAMAPK14CDK1BAXgossypolApoptosisObatoclax mesylateDIABLODOT1LMITFCD27GH1BCL2L11BAK1BBC3BAG1BADABT-7374-[4-[[2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohexenyl]methyl]-1-piperazinyl]-N-[4-[[(2R)-4-(4-morpholinyl)-1-(phenylthio)butan-2-yl]amino]-3-(trifluoromethylsulfonyl)phenyl]sulfonylbenzamideBECN1HMOX1SOD1CYCSNOTCH1GLI1/GLI2RHOXF1GbetaRBM10SMAD3Cell_deathTP53NR4A3NOXA1A5/b1 integrinHTRA2FOXA1CREB1venetoclaxHRKNOTCHPOLR1HNPTX1N-[4-(2-tert-butylphenyl)sulfonylphenyl]-2,3,4-trihydroxy-5-[(2-propan-2-ylphenyl)methyl]benzamideMYCT1Obatoclax

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▶Modifications Tables

Relations
Regulator
Mechanism
target
score ℹ
+ MAPK8up-regulates img/direct-activation.png phosphorylation BCL2 0.571
Identifier Residue Sequence Organism Cell Line
SIGNOR-179088 Ser70 RDPVARTsPLQTPAA Homo sapiens
pmid sentence
Together, our findings demonstrate that jnk1-mediated multisite phosphorylation of bcl-2 stimulates starvation-induced autophagy by disrupting the bcl-2/beclin 1 complex.
Identifier Residue Sequence Organism Cell Line
SIGNOR-72125 Ser70 RDPVARTsPLQTPAA Homo sapiens
pmid sentence
G(2)/m-phase cells proved more susceptible to death signals, and phosphorylation of bcl-2 appeared to be responsible, as a ser70ala substitution restored resistance to apoptosis. We noted that ask1 and jnk1 were normally activated at g(2)/m phase, and jnk was capable of phosphorylating bcl-2..
Publications: 2 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, COVID-19 Causal Network
+ MAPK3up-regulates img/direct-activation.png phosphorylation BCL2 0.548
Identifier Residue Sequence Organism Cell Line
SIGNOR-74935 Ser70 RDPVARTsPLQTPAA Homo sapiens
pmid sentence
Erk1 and erk2 directly phosphorylate bcl2 exclusively at ser-70 p44mapk/extracellular signal-regulated kinase 1 (erk1) and p42 mapk/erk2 are activated by il-3, colocalize with mitochondrial bcl2, and can directly phosphorylate bcl2 on ser-70 in a stauro-resistant manner both in vitro and in vivo molecular association.
Publications: 1 Organism: Homo Sapiens
+ ERK1/2up-regulates quantity by stabilization img/direct-activation.png phosphorylation BCL2 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-244501 Ser70 RDPVARTsPLQTPAA Chlorocebus aethiops COS Cell
pmid sentence
Erk1 and erk2 directly phosphorylate bcl2 exclusively at ser-70.
Identifier Residue Sequence Organism Cell Line
SIGNOR-244505 Ser87 AAAGPALsPVPPVVH Homo sapiens HeLa Cell
pmid sentence
The results of this study reveal the following novel findings: destruction of the three putative MAP kinase sites at positions 56, 74, and 87 results in ubiquitination and subsequent degradation of the protein. Progressive inactivation of these MAP kinase sites revealed that Bcl-2 stability is mainly regulated by phosphorylation at Thr74 and Ser87, with Ser87 phosphorylation playing a predominant role. TNF-α or the MAP kinase-specific inhibitor PD98059 diminishes Ser87 phosphorylation of Bcl-2 in vivo, while activated ERK2 induces phosphorylation of Bcl-2 in vivo and in vitro.
Identifier Residue Sequence Organism Cell Line
SIGNOR-244610 Thr56 FSSQPGHtPHPAASR Homo sapiens
pmid sentence
The results of this study reveal the following novel findings: destruction of the three putative MAP kinase sites at positions 56, 74, and 87 results in ubiquitination and subsequent degradation of the protein. Progressive inactivation of these MAP kinase sites revealed that Bcl-2 stability is mainly regulated by phosphorylation at Thr74 and Ser87.
Identifier Residue Sequence Organism Cell Line
SIGNOR-244494 Thr74 ARTSPLQtPAAPGAA Homo sapiens HeLa Cell
pmid sentence
The results of this study reveal the following novel findings: destruction of the three putative MAP kinase sites at positions 56, 74, and 87 results in ubiquitination and subsequent degradation of the protein. Progressive inactivation of these MAP kinase sites revealed that Bcl-2 stability is mainly regulated by phosphorylation at Thr74 and Ser87, with Ser87 phosphorylation playing a predominant role. TNF-α or the MAP kinase-specific inhibitor PD98059 diminishes Ser87 phosphorylation of Bcl-2 in vivo, while activated ERK2 induces phosphorylation of Bcl-2 in vivo and in vitro.
Publications: 4 Organism: Chlorocebus Aethiops, Homo Sapiens
Pathways:Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, AML_TRIPLETS, COVID-19 Causal Network, Colorectal Carcinoma, FLT3-ITD signaling, Inhibition of Apoptosis, Malignant Melanoma, Triple mutant AML, NPM1_new, Non-small-cell lung cancer (NSCLC), SARS-CoV MAPK PERTURBATION
+ JNKup-regulates activity img/direct-activation.png phosphorylation BCL2 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-261133 Ser70 RDPVARTsPLQTPAA in vitro
pmid sentence
JNK1 directly phosphorylates Bcl2 at Ser70 in vitro and co-localizes with Bcl2 in mitochondrial membranes in vivo.
Publications: 1 Organism: In Vitro
Pathways:COVID-19 Causal Network, FLT3-ITD signaling, SARS-CoV MAPK PERTURBATION
+ PPP2R5Bdown-regulates img/direct_inhibition.png dephosphorylation BCL2 0.312
Identifier Residue Sequence Organism Cell Line
SIGNOR-181559 Ser70 RDPVARTsPLQTPAA Homo sapiens
pmid sentence
Pp2a directly interacts with the bh4 domain of bcl2 as a docking site to potentially bridge pp2a to bcl2's flexible loop domain containing the target serine 70 phosphorylation site.
Publications: 1 Organism: Homo Sapiens
+ MAPK1up-regulates quantity by stabilization img/direct-activation.png phosphorylation BCL2 0.54
Identifier Residue Sequence Organism Cell Line
SIGNOR-219217 Ser70 RDPVARTsPLQTPAA Chlorocebus aethiops COS Cell
pmid sentence
Erk1 and erk2 directly phosphorylate bcl2 exclusively at ser-70.
Identifier Residue Sequence Organism Cell Line
SIGNOR-74919 Ser70 RDPVARTsPLQTPAA Homo sapiens HeLa Cell
pmid sentence
Phosphorylation of the map kinase sites in bcl-2, thr56, thr74, and ser87, is sufficient to inhibit tnf--induced degradation. p44mapk/extracellular signal-regulated kinase 1 (erk1) and p42 mapk/erk2 are activated by il-3, colocalize with mitochondrial bcl2, and can directly phosphorylate bcl2 on ser-70 in a stauro-resistant manner both_ in vitro_ and_ in vivo.
Identifier Residue Sequence Organism Cell Line
SIGNOR-74931 Ser87 AAAGPALsPVPPVVH Homo sapiens HeLa Cell
pmid sentence
Phosphorylation of the map kinase sites in bcl-2, thr56, thr74, and ser87, is sufficient to inhibit tnf--induced degradation.
Identifier Residue Sequence Organism Cell Line
SIGNOR-74923 Thr56 FSSQPGHtPHPAASR Homo sapiens
pmid sentence
Phosphorylation of the map kinase sites in bcl-2, thr56, thr74, and ser87, is sufficient to inhibit tnf--induced degradation. p44mapk/extracellular signal-regulated kinase 1 (erk1) and p42 mapk/erk2 are activated by il-3, colocalize with mitochondrial bcl2, and can directly phosphorylate bcl2 on ser-70 in a stauro-resistant manner both_ in vitro_ and_ in vivo.
Identifier Residue Sequence Organism Cell Line
SIGNOR-74927 Thr74 ARTSPLQtPAAPGAA Homo sapiens HeLa Cell
pmid sentence
In endothelial cells, tumor necrosis factor alpha (tnf-alpha) induces dephosphorylation and subsequent ubiquitin-dependent degradation of the antiapoptotic protein bcl-2. Here, we investigate the role of different putative phosphorylation sites to facilitate bcl-2 degradation
Publications: 5 Organism: Chlorocebus Aethiops, Homo Sapiens
+ PRKCAup-regulates img/direct-activation.png phosphorylation BCL2 0.353
Identifier Residue Sequence Organism Cell Line
SIGNOR-60120 Ser70 RDPVARTsPLQTPAA Homo sapiens Leukemia Cell
pmid sentence
Purified pkca can efficiently and directly phosphorylate bcl2 at serine 70
Publications: 1 Organism: Homo Sapiens
+ p38down-regulates activity img/direct_inhibition.png phosphorylation BCL2 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-260450 Ser87 AAAGPALsPVPPVVH Homo sapiens
pmid sentence
The protein's reduced antiapoptotic capacity was related to phosphorylation of its threonine 56 and serine 87 residues by virally activated p38mapk
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, SARS-COV APOPTOSIS, SARS-CoV MAPK PERTURBATION
+ MAPK8down-regulates activity img/direct_inhibition.png phosphorylation BCL2 0.571
Identifier Residue Sequence Organism Cell Line
SIGNOR-48038 Ser87 AAAGPALsPVPPVVH Homo sapiens
pmid sentence
Jnk1-mediated phosphorylation of bcl-2 regulates starvation-induced autophagy.
Identifier Residue Sequence Organism Cell Line
SIGNOR-179092 Ser87 AAAGPALsPVPPVVH Homo sapiens
pmid sentence
Jnk1-mediated phosphorylation of bcl-2 regulates starvation-induced autophagy.
Publications: 2 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, COVID-19 Causal Network
+ PPP2CBup-regulates activity img/direct-activation.png dephosphorylation BCL2 0.375
Identifier Residue Sequence Organism Cell Line
SIGNOR-248589 Ser87 AAAGPALsPVPPVVH Homo sapiens
pmid sentence
The phosphorylation of Bcl-2 resulted in a reduction in anti-apoptotic function, implying that dephosphorylation promoted the anti-apoptotic activity of Bcl-2 protein in human tumor cell lines. Thus, the present findings suggest that ERK and PP2A are physiological regulators of Bcl-2 phosphorylation, and these enzymes exert an influence on the anti-apoptotic function of Bcl-2.phosphorylation of Bcl2 at Ser70 is proposed to be a dynamic process regulated by the sequential action of an agonist-activated Bcl2 kinase and PP2A.
Publications: 1 Organism: Homo Sapiens
+ PPP2CAup-regulates activity img/direct-activation.png dephosphorylation BCL2 0.462
Identifier Residue Sequence Organism Cell Line
SIGNOR-248624 Ser87 AAAGPALsPVPPVVH Homo sapiens
pmid sentence
The phosphorylation of Bcl-2 resulted in a reduction in anti-apoptotic function, implying that dephosphorylation promoted the anti-apoptotic activity of Bcl-2 protein in human tumor cell lines. Thus, the present findings suggest that ERK and PP2A are physiological regulators of Bcl-2 phosphorylation, and these enzymes exert an influence on the anti-apoptotic function of Bcl-2.phosphorylation of Bcl2 at Ser70 is proposed to be a dynamic process regulated by the sequential action of an agonist-activated Bcl2 kinase and PP2A.
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network
+ MAPK14down-regulates activity img/direct_inhibition.png phosphorylation BCL2 0.337
Identifier Residue Sequence Organism Cell Line
SIGNOR-184936 Ser87 AAAGPALsPVPPVVH Homo sapiens
pmid sentence
The protein's reduced antiapoptotic capacity was related to phosphorylation of its threonine 56 and serine 87 residues by virally activated p38mapk
Identifier Residue Sequence Organism Cell Line
SIGNOR-146786 Thr56 FSSQPGHtPHPAASR Homo sapiens
pmid sentence
Bcl-2 phosphorylation by p38 mapkin this study, we identify, by using mass spectrometry techniques and specific anti-phosphopeptide antibodies, ser(87) and thr(56) as the bcl-2 residues phosphorylated by p38 mapk and show that phosphorylation of these residues is always associated with a decrease in the antiapoptotic potential of bcl-2 protein.
Publications: 2 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling
+ CDK1up-regulates activity img/direct-activation.png phosphorylation BCL2 0.349
Identifier Residue Sequence Organism Cell Line
SIGNOR-76837 Thr56 FSSQPGHtPHPAASR Homo sapiens
pmid sentence
Using synthetic peptides and mutant cell lines, we identified threonine 56, one of two consensus sites for cdc2 within the bcl-2 sequence, as a residue phosphorylated by cdc2. Mutation at threonine 56 abrogated the cell cycle inhibitory effect of bcl-2 without affecting anti-apoptotic function.Taken together, our present findings indicate that phosphorylation of bcl-2 at threonine 56 by cdc2 is required for bcl-2-mediated cell cycle inhibition, which may have some roles during mitosis in the normal cell cycle.
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, KIT in AML
+ MAPK3up-regulates quantity by stabilization img/direct-activation.png phosphorylation BCL2 0.548
Identifier Residue Sequence Organism Cell Line
SIGNOR-74939 Thr56 FSSQPGHtPHPAASR Homo sapiens
pmid sentence
Phosphorylation of the map kinase sites in bcl-2, thr56, thr74, and ser87, is sufficient to inhibit tnf--induced degradation. p44mapk/extracellular signal-regulated kinase 1 (erk1) and p42 mapk/erk2 are activated by il-3, colocalize with mitochondrial bcl2, and can directly phosphorylate bcl2 on ser-70 in a stauro-resistant manner both_ in vitro_ and_ in vivo.
Identifier Residue Sequence Organism Cell Line
SIGNOR-74943 Thr74 ARTSPLQtPAAPGAA Homo sapiens
pmid sentence
The results of this study reveal the following novel findings: destruction of the three putative MAP kinase sites at positions 56, 74, and 87 results in ubiquitination and subsequent degradation of the protein. Progressive inactivation of these MAP kinase sites revealed that Bcl-2 stability is mainly regulated by phosphorylation at Thr74 and Ser87, with Ser87 phosphorylation playing a predominant role. TNF-α or the MAP kinase-specific inhibitor PD98059 diminishes Ser87 phosphorylation of Bcl-2 in vivo, while activated ERK2 induces phosphorylation of Bcl-2 in vivo and in vitro.
Publications: 2 Organism: Homo Sapiens
+ MAPK8down-regulates img/direct_inhibition.png phosphorylation BCL2 0.571
Identifier Residue Sequence Organism Cell Line
SIGNOR-179096 Thr69 SRDPVARtSPLQTPA Homo sapiens
pmid sentence
Together, our findings demonstrate that jnk1-mediated multisite phosphorylation of bcl-2 stimulates starvation-induced autophagy by disrupting the bcl-2/beclin 1 complex.
Identifier Residue Sequence Organism Cell Line
SIGNOR-72361 Thr69 SRDPVARtSPLQTPA Homo sapiens
pmid sentence
G(2)/m-phase cells proved more susceptible to death signals, and phosphorylation of bcl-2 appeared to be responsible, as a ser70ala substitution restored resistance to apoptosis. We noted that ask1 and jnk1 were normally activated at g(2)/m phase, and jnk was capable of phosphorylating bcl-2..
Identifier Residue Sequence Organism Cell Line
SIGNOR-72364 Homo sapiens
pmid sentence
Jnk was capable of phosphorylating bcl-2. Phosphorylation of bcl-2 inactivates the molecule
Publications: 3 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, COVID-19 Causal Network
+ BAXdown-regulates activity img/direct_inhibition.png binding BCL2 0.626
Identifier Residue Sequence Organism Cell Line
SIGNOR-249612
pmid sentence
Bax shows extensive amino acid homology with Bcl-2 and forms homodimers and heterodimers with Bcl-2 in vivo. When Bax predominates, programed cell death is accelerated, and the death repressor activity of Bcl-2 is countered.
Publications: 1
Pathways:Alzheimer, Acute Myeloid Leukemia, MLL fusion protein in AML, COVID-19 Causal Network, Death Receptor Signaling, FLT3-ITD signaling, Inhibition of Apoptosis, Mitochondrial Control of Apoptosis, Malignant Melanoma, p53 in cancer, SARS-COV APOPTOSIS
+ gossypoldown-regulates img/direct_inhibition.png chemical inhibition BCL2 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-200469 Homo sapiens
pmid sentence
Bcl-2 inhibitors physically antagonize their anti-apoptotic actions to create a synergistic effect. Numerous compounds have been specifically developed or identified as bcl-2 inhibitors. These compounds include abt-737 and abt-263, obatoclax, gossypol.
Publications: 1 Organism: Homo Sapiens
+ BCL2down-regulates img/indirect_inhibition.png Apoptosis 0.7
Identifier Residue Sequence Organism Cell Line
SIGNOR-249611 Homo sapiens
pmid sentence
Bcl-2 functions to inhibit apoptosis in a variety of in vitro and in vivo experiments, suggesting interference with a central mechanism of apoptosis
Publications: 1 Organism: Homo Sapiens
Pathways:Alzheimer, Acute Myeloid Leukemia, BCR-ABL in AML, DNMT3A in AML, FLT3 in AML, KIT in AML, miRNA in AML, MLL fusion protein in AML, AML_TRIPLETS, COVID-19 Causal Network, Colorectal Carcinoma, Death Receptor Signaling, FLT3-ITD signaling, Inhibition of Apoptosis, Mitochondrial Control of Apoptosis, Malignant Melanoma, Triple mutant AML, NPM1_new, p53 in cancer, SARS-COV APOPTOSIS, SARS-CoV MAPK PERTURBATION
+ Obatoclax mesylatedown-regulates activity img/direct_inhibition.png chemical inhibition BCL2 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-262022 in vitro
pmid sentence
Obatoclax and its predecessor analogs bind to BCL-2, BCL-XL, BCL-w, BCL-B, BFL-1, and MCL-1 in vitro
Publications: 1 Organism: In Vitro
+ BCL2down-regulates img/indirect_inhibition.png DIABLO 0.48
Identifier Residue Sequence Organism Cell Line
SIGNOR-88885 Homo sapiens
pmid sentence
Bcl- confers protection to apoptosis by interference with bax/bak-mediated release of the pro-apoptotic mitochodrial factors smac/diablo and htra2/omi
Publications: 1 Organism: Homo Sapiens
Pathways:Death Receptor Signaling
+ DOT1Lup-regulates quantity by expression img/indirect-activation.png transcriptional regulation BCL2 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-255880 Homo sapiens
pmid sentence
Previously, we found that MLL-AF4 binds to the BCL-2 gene and directly activates it through DOT1L recruitment and increased H3K79me2/3 levels. MLL-AF4 directly controls the active transcription of both BCL-2 and MCL-1 […]. Of all the BCL-2 family members, only BCL-2 and MCL-1 are directly activated by MLL-AF4.
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, MLL fusion protein in AML
+ MITFup-regulates quantity by expression img/direct-activation.png transcriptional regulation BCL2 0.462
Identifier Residue Sequence Organism Cell Line
SIGNOR-249618
pmid sentence
MITF directly occupies the BCL2 promoter in vivo and this suggest that BCL2 may be a direct transcriptional target of MITF
Publications: 1
Pathways:Malignant Melanoma
+ CD27up-regulates quantity by expression img/indirect-activation.png transcriptional regulation BCL2 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-93317 Homo sapiens
pmid sentence
Cd40 ligation up-regulated bcl-2 and bcl-xl as much as 9.7- (p < 0.01) and 6.8-fold (p < 0.01), respectively (fig. 2, b and c). Under similar conditions, cd27 ligation also up-regulated bcl-2 and bcl-xl as much as 5.0- (p < 0.01) and 3.9-fold (p < 0.01), respectively.
Publications: 1 Organism: Homo Sapiens
+ GH1up-regulates quantity by expression img/direct-activation.png transcriptional regulation BCL2 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-261628 Homo sapiens MCF-10A Cell
pmid sentence
Autocrine hGH increased the transcription and subsequent mRNA level and protein expression of c-Myc, Cyclin D1, and Bcl-2 in human mammary epithelial cells
Publications: 1 Organism: Homo Sapiens
+ BCL2L11down-regulates activity img/direct_inhibition.png binding BCL2 0.814
Identifier Residue Sequence Organism Cell Line
SIGNOR-133820 Homo sapiens HEK-293 Cell
pmid sentence
Apoptosis is initiated when Bcl-2 and its prosurvival relatives are engaged by proapoptotic BH3-only proteins via interaction of its BH3 domain with a groove on the Bcl-2-like proteins. These interactions have been considered promiscuous, but our analysis of the affinity of eight BH3 peptides for five Bcl-2-like proteins has revealed that the interactions vary over 10,000-fold in affinity, and accordingly, only certain protein pairs associate inside cells. Bim and Puma potently engaged all the prosurvival proteins comparably. Bad, however, bound tightly to Bcl-2, Bcl-xL, and Bcl-w but only weakly to A1 and not to Mcl-1.
Identifier Residue Sequence Organism Cell Line
SIGNOR-178676 Homo sapiens HEK-293 Cell
pmid sentence
We show that mutation of the phosphorylation site Thr-112 causes decreased binding of Bim to the antiapoptotic protein Bcl2 and can increase cell survival.
Publications: 2 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, Inhibition of Apoptosis, Mitochondrial Control of Apoptosis, SARS-COV APOPTOSIS
+ BCL2down-regulates img/direct_inhibition.png binding BAK1 0.668
Identifier Residue Sequence Organism Cell Line
SIGNOR-55546 Homo sapiens
pmid sentence
Bcl-2 bind to bax or five other pro-apoptotic relatives (bak, bad, bik, bid or bim)
Identifier Residue Sequence Organism Cell Line
SIGNOR-152980 Homo sapiens
pmid sentence
Bax is held in check by mcl1, bcl-2, and either bcl2l1 or bcl2l2, or by all four. They bind a primed conformer of bak or bax bax/bak are kept in check by the pro-survival bcl-2 family members and also proposes that for apoptotic death to occur, all pro-survival bcl-2-like proteins present within a given cell need to be neutralised by bh3-only proteins, thereby derepressing bax/bak
Publications: 2 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, MLL fusion protein in AML, Malignant Melanoma, Non-small-cell lung cancer (NSCLC)
+ BBC3down-regulates activity img/direct_inhibition.png binding BCL2 0.654
Identifier Residue Sequence Organism Cell Line
SIGNOR-133808 Homo sapiens HEK-293 Cell
pmid sentence
Only bimbh3 and bbc3 had comparable strong affinitiesfor all the prosurvival proteins. The members that promote cell survival, including mammalian bcl-2, bcl-xl,bcl-w, mcl-1, and a1.
Identifier Residue Sequence Organism Cell Line
SIGNOR-109506 Homo sapiens U2-OS Cell
pmid sentence
Puma localizes to the mitochondria, interacts with bcl-2, and function to induce cytochrome c release
Publications: 2 Organism: Homo Sapiens
Pathways:Death Receptor Signaling, Mitochondrial Control of Apoptosis
+ BAG1up-regulates activity img/direct-activation.png binding BCL2 0.421
Identifier Residue Sequence Organism Cell Line
SIGNOR-254118 Homo sapiens JURKAT Cell
pmid sentence
Cloning and functional analysis of BAG-1: A novel Bcl-2-binding protein with anti-cell death activity|
Publications: 1 Organism: Homo Sapiens
+ BADdown-regulates activity img/direct_inhibition.png relocalization BCL2 0.796
Identifier Residue Sequence Organism Cell Line
SIGNOR-133756 Homo sapiens HEK-293 Cell
pmid sentence
Apoptosis is initiated when Bcl-2 and its prosurvival relatives are engaged by proapoptotic BH3-only proteins via interaction of its BH3 domain with a groove on the Bcl-2-like proteins. These interactions have been considered promiscuous, but our analysis of the affinity of eight BH3 peptides for five Bcl-2-like proteins has revealed that the interactions vary over 10,000-fold in affinity, and accordingly, only certain protein pairs associate inside cells. Bim and Puma potently engaged all the prosurvival proteins comparably. Bad, however, bound tightly to Bcl-2, Bcl-xL, and Bcl-w but only weakly to A1 and not to Mcl-1.
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, COVID-19 Causal Network, FLT3-ITD signaling, Inhibition of Apoptosis, Mitochondrial Control of Apoptosis, Malignant Melanoma, SARS-COV APOPTOSIS
+ ABT-737down-regulates img/direct_inhibition.png chemical inhibition BCL2 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-151781 Homo sapiens Leukemia Cell, B-lymphocyte, Lymphoma Cell
pmid sentence
A cell-permeant compound, abt-737, binds with high affinity to bcl2, bcl2l1, and bcl2l2, antagonizes their antiapoptotic function, and induces apoptosis in select human tumor cell lines, primary patient-derived cells.
Identifier Residue Sequence Organism Cell Line
SIGNOR-189159 Homo sapiens
pmid sentence
Publications: 2 Organism: Homo Sapiens
+ 4-[4-[[2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohexenyl]methyl]-1-piperazinyl]-N-[4-[[(2R)-4-(4-morpholinyl)-1-(phenylthio)butan-2-yl]amino]-3-(trifluoromethylsulfonyl)phenyl]sulfonylbenzamidedown-regulates img/direct_inhibition.png chemical inhibition BCL2 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-200460 Homo sapiens
pmid sentence
Bcl-2 inhibitors physically antagonize their anti-apoptotic actions to create a synergistic effect. Numerous compounds have been specifically developed or identified as bcl-2 inhibitors. These compounds include abt-737 and abt-263, obatoclax, gossypol.
Identifier Residue Sequence Organism Cell Line
SIGNOR-189150 Homo sapiens
pmid sentence
Publications: 2 Organism: Homo Sapiens
+ BCL2down-regulates img/direct_inhibition.png binding BECN1 0.734
Identifier Residue Sequence Organism Cell Line
SIGNOR-156941 Homo sapiens
pmid sentence
In mammalian cells, the antiapoptotic protein, bcl-2, binds to beclin 1 during nonstarvation conditions and inhibits its autophagy function.
Identifier Residue Sequence Organism Cell Line
SIGNOR-179084 Homo sapiens
pmid sentence
In mammalian cells, the antiapoptotic protein, bcl-2, binds to beclin 1 during nonstarvation conditions and inhibits its autophagy function.
Identifier Residue Sequence Organism Cell Line
SIGNOR-154477 Homo sapiens
pmid sentence
In mammalian cells, the antiapoptotic protein, bcl-2, binds to beclin 1 during nonstarvation conditions and inhibits its autophagy function.
Publications: 3 Organism: Homo Sapiens
Pathways:Autophagy
+ HMOX1up-regulates quantity by expression img/indirect-activation.png transcriptional regulation BCL2 0.251
Identifier Residue Sequence Organism Cell Line
SIGNOR-256303 Homo sapiens
pmid sentence
The results of the present study indicated that knockdown of HMOX-1 significantly enhanced doxorubicin-induced apoptosis and downregulated the expression of Bcl-2 and Bcl-xL in breast cancer cells.
Publications: 1 Organism: Homo Sapiens
+ SOD1up-regulates activity img/direct-activation.png binding BCL2 0.495
Identifier Residue Sequence Organism Cell Line
SIGNOR-262799 Homo sapiens
pmid sentence
Familial amyotrophic lateral sclerosis (ALS)-linked mutations in the copper-zinc superoxide dismutase (SOD1) gene cause motor neuron death in about 3% of ALS cases. While the wild-type (wt) protein is anti-apoptotic, mutant SOD1 promotes apoptosis.|We now demonstrate that both wt and mutant SOD1 bind the anti-apoptotic protein Bcl-2, providing evidence of a direct link between SOD1 and an apoptotic pathway. This interaction is evident in vitro and in vivo in mouse and human spinal cord.|These findings provide new insights into the anti-apoptotic function of SOD1 and suggest that entrapment of Bcl-2 by large SOD1 aggregates may deplete motor neurons of this anti-apoptotic protein.
Publications: 1 Organism: Homo Sapiens
Tissue: Spinal Cord
Pathways:Autophagy
+ BCL2down-regulates activity img/indirect_inhibition.png CYCS 0.636
Identifier Residue Sequence Organism Cell Line
SIGNOR-99063 Homo sapiens HeLa Cell
pmid sentence
Bcl-2 blocked the release of mitochondrial cytochrome c
Publications: 1 Organism: Homo Sapiens
Pathways:Alzheimer, COVID-19 Causal Network, Death Receptor Signaling, Mitochondrial Control of Apoptosis, SARS-COV APOPTOSIS
+ NOTCH1up-regulates quantity by expression img/indirect-activation.png transcriptional regulation BCL2 0.265
Identifier Residue Sequence Organism Cell Line
SIGNOR-149730 Homo sapiens T-lymphocyte
pmid sentence
Other notch target genes identi__ed in the thymoma cell line were dtx1 (gene for deltex1), i__-202, i__-204, i__-d3, adam19 (meltrinb).24 a number of other genes have been reported as being notch targets, including notch1 itself,28 nrarp in xenopus embryos,29 bcl2 in thymoma cells,30 ccnd1 (gene for cyclin d1) in a kidney cell line,31 dkn1a (gene for cyclindependent kinase inhibitor 1a (p21, cip1)) in keratinocytes32 and tcf3 (gene for e2a).
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, FLT3-ITD signaling
+ GLI1/GLI2up-regulates quantity by expression img/direct-activation.png transcriptional regulation BCL2 0.389
Identifier Residue Sequence Organism Cell Line
SIGNOR-269211 Homo sapiens PANC-1 Cell
pmid sentence
GLI1 and GLI2 were shown to co-immunoprecipitate in PANC1 pancreatic cancer cells and RMS13 rhabdomyosarcoma cells.|Chromatin immunoprecipitation showed that GLI1 and GLI2 occupied the same regions at the BCL2, MYCN and CCND1 promoters. Furthermore, depletion of GLI1 inhibited GLI2 occupancy at these promoters, suggesting that GLI1/GLI2 interaction is required for the recruitment of GLI2 to these sites. | RNAi knockdown of either GLI1 or GLI2 inhibited expression of many well-characterized GLI target genes (BCL2, MYCN, PTCH2, IL7 and CCND1) in PANC1 cells
Publications: 1 Organism: Homo Sapiens
+ RHOXF1up-regulates quantity by expression img/indirect-activation.png transcriptional regulation BCL2 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-268957
pmid sentence
ShRNA knock down of RHOXF1 resulted in significantly decreased BCL2 expression in both cell lines but no change in CASP8 expression.
Publications: 1
+ Gbetaup-regulates img/direct-activation.png phosphorylation BCL2 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-270064 Homo sapiens
pmid sentence
Erk1 and erk2 directly phosphorylate bcl2 exclusively at ser-70 p44mapk/extracellular signal-regulated kinase 1 (erk1) and p42 mapk/erk2 are activated by il-3, colocalize with mitochondrial bcl2, and can directly phosphorylate bcl2 on ser-70 in a stauro-resistant manner both in vitro and in vivo molecular association.
Publications: 1 Organism: Homo Sapiens
+ RBM10down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation BCL2 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-259151 Homo sapiens
pmid sentence
In this study, we report that RBM10 acts as a tumor suppressor in osteosarcoma via the inhibition of cell growth, cell migration and invasion and the induction of cell apoptosis by inhibiting Bcl-2, activating caspase-3, and producing TNF-α. We also found that RBM10 overexpression significantly inhibited the expression of Bcl-2 and induced the expression of caspase-3
Publications: 1 Organism: Homo Sapiens
+ SMAD3down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation BCL2 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-256294 Homo sapiens
pmid sentence
This protection is conferred by Smad3’s ability to promote apoptosis by repressing Bcl-2 transcription in vivo through a GC-rich element in the Bcl-2 promoter.
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, Colorectal Carcinoma
+ BCL2down-regulates img/indirect_inhibition.png Cell_death 0.7
Identifier Residue Sequence Organism Cell Line
SIGNOR-256637 Homo sapiens
pmid sentence
Bcl-2 functions to inhibit apoptosis in a variety of in vitro and in vivo experiments, suggesting interference with a central mechanism of apoptosis
Publications: 1 Organism: Homo Sapiens
+ TP53down-regulates activity img/direct_inhibition.png binding BCL2 0.743
Identifier Residue Sequence Organism Cell Line
SIGNOR-99712 Homo sapiens
pmid sentence
Mechanistic insights into the mitochondrial function of wtp53 came when it was realized that mitochondrially translocated p53 interacts directly with members of the Bcl-2 family, which are central in governing the induction of mitochondrial outer membrane permeabilization. In response to stress, wtp53 interacts with and neutralizes the anti-apoptotic members Bcl-xL and Bcl-2. This interaction stimulates MOMP and subsequent apoptosis
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, DNMT3A in AML, KIT in AML, miRNA in AML, AML_TRIPLETS, Colorectal Carcinoma, FLT3-ITD signaling, Mitochondrial Control of Apoptosis, Malignant Melanoma, Triple mutant AML, NPM1_new, Non-small-cell lung cancer (NSCLC), p53 in cancer
+ NR4A3down-regulates activity img/direct_inhibition.png binding BCL2 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-259399 Homo sapiens
pmid sentence
NR4A3 physically interacted with an anti-apoptotic Bcl-2 protein hence sequestering it from blunting apoptosis.
Publications: 1 Organism: Homo Sapiens
+ BCL2down-regulates activity img/direct_inhibition.png binding BAX 0.626
Identifier Residue Sequence Organism Cell Line
SIGNOR-36898 Homo sapiens B-lymphocyte, Lymphoma Cell
pmid sentence
Bcl-2 has the unique oncogenic role of extending cell survival by inhibiting a variety of apoptotic deaths. Bcl-2 exerts its action through heterodimerization with bax.
Publications: 1 Organism: Homo Sapiens
Pathways:Alzheimer, Acute Myeloid Leukemia, MLL fusion protein in AML, COVID-19 Causal Network, Death Receptor Signaling, FLT3-ITD signaling, Inhibition of Apoptosis, Mitochondrial Control of Apoptosis, Malignant Melanoma, p53 in cancer, SARS-COV APOPTOSIS
+ TP53down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation BCL2 0.743
Identifier Residue Sequence Organism Cell Line
SIGNOR-271677
pmid sentence
P53 suppresses the activation of the Bcl-2 promoter by the Brn-3a POU family transcription factor.
Publications: 1
Pathways:Acute Myeloid Leukemia, DNMT3A in AML, KIT in AML, miRNA in AML, AML_TRIPLETS, Colorectal Carcinoma, FLT3-ITD signaling, Mitochondrial Control of Apoptosis, Malignant Melanoma, Triple mutant AML, NPM1_new, Non-small-cell lung cancer (NSCLC), p53 in cancer
+ NOXA1down-regulates activity img/direct_inhibition.png BCL2 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-209684 Homo sapiens
pmid sentence
BH3-only proteins containing only a single BH domain and including Puma, Noxa, Bid and Bad as well as other factors are particularly important for such neutralisation, binding and regulating the anti-apoptotic Bcl-2 proteins to promote apoptosis
Publications: 1 Organism: Homo Sapiens
Pathways:Mitochondrial Control of Apoptosis
+ Obatoclax mesylatedown-regulates img/direct_inhibition.png chemical inhibition BCL2 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-194952 Homo sapiens
pmid sentence
Publications: 1 Organism: Homo Sapiens
+ A5/b1 integrinup-regulates quantity img/indirect-activation.png BCL2 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-253310
pmid sentence
Previous reports indicated that the prosurvival signal mediated through α5β1-fibronectin interactions was due to increased Bcl-2 levels
Publications: 1
+ BCL2down-regulates img/indirect_inhibition.png HTRA2 0.253
Identifier Residue Sequence Organism Cell Line
SIGNOR-89189 Homo sapiens
pmid sentence
Bcl- confers protection to apoptosis by interference with bax/bak-mediated release of the pro-apoptotic mitochodrial factors smac/diablo and htra2/omi
Publications: 1 Organism: Homo Sapiens
+ FOXA1down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation BCL2 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-161448 Homo sapiens
pmid sentence
Foxa1 overexpression decreased the expression of bcl2, while foxa1 depletion increased the expression of bcl2
Publications: 1 Organism: Homo Sapiens
+ CREB1up-regulates quantity by expression img/indirect-activation.png transcriptional regulation BCL2 0.447
Identifier Residue Sequence Organism Cell Line
SIGNOR-76558 Rattus norvegicus PC-12 Cell
pmid sentence
Creb activity by akt signaling leads to increased bcl-2 promoter activity and cell survival.
Identifier Residue Sequence Organism Cell Line
SIGNOR-43927 Homo sapiens B-lymphocyte, RAMOS Cell
pmid sentence
Induction of bcl-2 expression by phosphorylated CREB proteins during B-cell activation and rescue from apoptosis
Publications: 2 Organism: Rattus Norvegicus, Homo Sapiens
Pathways:COVID-19 Causal Network, FLT3-ITD signaling, Inhibition of Apoptosis, Malignant Melanoma, SARS-CoV MAPK PERTURBATION
+ venetoclaxdown-regulates activity img/direct_inhibition.png chemical inhibition BCL2 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-261938 Homo sapiens
pmid sentence
Here we report the re-engineering of navitoclax to create a highly potent, orally bioavailable and BCL-2-selective inhibitor, ABT-199. This compound inhibits the growth of BCL-2-dependent tumors in vivo and spares human platelets. These data indicate that selective pharmacological inhibition of BCL-2 shows promise for the treatment of BCL-2-dependent hematological cancers.
Publications: 1 Organism: Homo Sapiens
+ HRKdown-regulates img/direct_inhibition.png binding BCL2 0.479
Identifier Residue Sequence Organism Cell Line
SIGNOR-47794 Homo sapiens
pmid sentence
Hrk, physically interacts with the death-repressor proteins bcl2 and bcl2l1. Hrk activates cell death at least in part by interacting with and inhibiting the protection afforded by bcl2 and bcl2l1.
Publications: 1 Organism: Homo Sapiens
+ NOTCHup-regulates quantity by expression img/indirect-activation.png transcriptional regulation BCL2 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-254344 Homo sapiens T-lymphocyte
pmid sentence
Addition of jag-1 peptide induced ikkalpha mediated nf-kappab activation, as well as increased ppargamma expression.
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia
+ POLR1Hup-regulates quantity by expression img/indirect-activation.png transcriptional regulation BCL2 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-259908 Homo sapiens
pmid sentence
ZNRD1 could significantly up-regulate the expression of P-gp, Bcl-2, and the transcription of the MDR1 gene but not alter the expression of MDR-associated protein, glutathione S-transferase activity, or intracellular glutathione content in leukemia cells.
Publications: 1 Organism: Homo Sapiens
+ NPTX1down-regulates quantity img/indirect_inhibition.png BCL2 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-260412 Homo sapiens MHCC-97 Cell, SMMC-7721 Cell
pmid sentence
We found that the protein levels of BCL2-associated agonist of cell death (BAD) and BCL2-associated X protein (BAX) were increased in NPTX1-overexpressing SMMC-7721 and MHCC-97h cells relative to control cells. In contrast, decreased levels of myeloid cell leukemia sequence 1 (Mcl-1) and B-cell lymphoma-2 (Bcl-2) were found in NPTX1-overexpressing SMMC-7721 and MHCC-97h cells relative to control
Publications: 1 Organism: Homo Sapiens
+ N-[4-(2-tert-butylphenyl)sulfonylphenyl]-2,3,4-trihydroxy-5-[(2-propan-2-ylphenyl)methyl]benzamidedown-regulates img/direct_inhibition.png chemical inhibition BCL2 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-207459 Homo sapiens
pmid sentence
Publications: 1 Organism: Homo Sapiens
+ MYCT1down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation BCL2 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-261735 Homo sapiens
pmid sentence
MYCT1 overexpression significantly inhibited cell proliferation, arrested cell cycle at G0/G1 phase, and downregulated the expression of cyclins D and E. Moreover, MYCT1 overexpression triggered apoptosis in AML cells, which was accompanied by enhanced cleavage of caspase-3 and -9, upregulated expression of B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax), and downregulated Bcl-2.
Publications: 1 Organism: Homo Sapiens
+ Obatoclaxdown-regulates img/direct_inhibition.png chemical inhibition BCL2 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-200478 Homo sapiens
pmid sentence
Bcl-2 inhibitors physically antagonize their anti-apoptotic actions to create a synergistic effect. Numerous compounds have been specifically developed or identified as bcl-2 inhibitors. These compounds include abt-737 and abt-263, obatoclax, gossypol.
Publications: 1 Organism: Homo Sapiens
+ CDK1down-regulates activity img/direct_inhibition.png phosphorylation BCL2 0.349
Identifier Residue Sequence Organism Cell Line
SIGNOR-267987 Homo sapiens KB-3-1 Cell
pmid sentence
Cyclin-Dependent Kinase 1-Mediated Bcl-xL/Bcl-2 Phosphorylation Acts as a Functional Link Coupling Mitotic Arrest and Apoptosis|These findings suggest a model whereby a switch in the duration of CDK1 activation, from transient during mitosis to sustained during mitotic arrest, dramatically increases the extent of Bcl-xL/Bcl-2 phosphorylation, resulting in inactivation of their antiapoptotic function. Thus, phosphorylation of antiapoptotic Bcl-2 proteins acts as a sensor for CDK1 signal duration and as a functional link coupling mitotic arrest to apoptosis.
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, KIT in AML
+ BCL2L11down-regulates img/direct_inhibition.png binding BCL2 0.814
Identifier Residue Sequence Organism Cell Line
SIGNOR-133823 Homo sapiens
pmid sentence
Bim can induce apoptosis by interacting with anti-apoptotic members of the bcl2 family, including bcl2, bcl-xl and mcl-1.. Bim binds prosurvival proteins comparably. The members that promote cell survival, including mammalian bcl-2, bcl-xl,bcl-w, mcl-1, and a1
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, Inhibition of Apoptosis, Mitochondrial Control of Apoptosis, SARS-COV APOPTOSIS
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