Recombinant Mouse Bcl-2-like protein 1 (Bcl2l1)
Description
Introduction
Bcl-2-like protein 1 (Bcl2l1), also known as Bfl-1 or A1, is a member of the Bcl-2 family of proteins that regulate apoptosis . These proteins are crucial in controlling cell survival and death pathways, and their dysregulation is implicated in various diseases, including cancer . Recombinant Mouse Bcl-2-like protein 1 is a form of the protein produced using recombinant DNA technology, typically in bacterial or cell culture systems, for research purposes .
Production and Characteristics
Recombinant Mouse Bcl-2(1-203), which lacks the COOH-terminal hydrophobic tail, can be produced in bacterial inclusion bodies, solubilized, and refolded through dialysis, resulting in a monomeric protein in a nondenaturing solution . This recombinant protein has demonstrated activity in protecting mouse T hybridoma cells from glucocorticoid-induced apoptosis . Limited proteolysis experiments have identified a protease-sensitive region between the BH3 and BH4 homology domains of Bcl-2(1-203) .
Role in Cancer
Bcl2l1 is implicated in the development and progression of various cancers .
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Anti-Apoptotic Function: As an anti-apoptotic protein, Bcl2l1 prevents programmed cell death, allowing cancer cells to survive and proliferate .
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Overexpression and Amplification: Bcl2l1 is often overexpressed or amplified in cancer cells, contributing to their resistance to apoptosis . For example, amplification of BCL2L1 was detected in 10.7% of gastric cancer cases analyzed by aCGH .
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Drug Resistance: Bcl2l1 can confer resistance to anticancer drugs. For instance, the β-catenin/BCL2L1 axis may play a vital role in cisplatin resistance .
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Therapeutic Target: Given its role in cancer cell survival, Bcl2l1 is a potential therapeutic target. Inhibiting Bcl2l1 can promote apoptosis in cancer cells, either alone or in combination with other therapies .
Interactions and Inhibitors
Bcl2l1 interacts with other proteins in the Bcl-2 family, such as Mcl-1 and Bcl-xL, to regulate apoptosis .
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Dual Inhibitors: Some compounds can inhibit multiple anti-apoptotic proteins simultaneously. For example, 2,5-substituted benzoic acid derivatives have been designed to bind to both Mcl-1 and Bfl-1, with some showing appreciable selectivity over Bcl-2/Bcl-xL . Compound 1 shows equipotent binding to both Mcl-1 and Bfl-1 proteins with 2- and 3-fold improvement, respectively, in comparison with 19SR .
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Specific Inhibitors: BH3 mimetics, such as ABT-737, can inhibit Bcl2l1 and induce apoptosis, particularly in cells with BCL2L1 amplification .
Table 1. Binding affinities of 2,5-Substituted Benzoic Acid Derivatives to Mcl-1 and Bfl-1 Proteins
| Compound | R1 | Mcl-1 Ki (μM) | Bfl-1 Ki (μM) |
|---|---|---|---|
| 1 | 1.5 ± 0.3 | 1.6 ± 0.2 | |
| 2 | H | 47.8 ± 3.9 | >100 |
| 3 | 2.6 ± 0.4 | 3.0 ± 0.4 | |
| 4 | 13.1 ± 2.4 | 14.8 ± 2.7 | |
| 5 | 32.8 ± 4.9 | >70 | |
| 6 | 4.7 ± 0.7 | 3.8 ± 1.1 | |
| 7 | 70.4 ± 5.4 | >70 | |
| 8 | 19.0 ± 1.2 | 62.0 ± 1.8 | |
| 9 | 6.1 ± 1.0 | 10.6 ± 1.2 | |
| Compound | R2 | Mcl-1 Ki (μM) | Bfl-1 Ki (μM) |
| 10 | H | 3.4 ± 0.4 | 3.7 ± 0.4 |
| 11 | 2.7 ± 0.6 | 4.6 ± 0.5 |
Clinical Significance
The ATP1A1/BCL2L1 ratio is specifically associated with myelomonocytic and monocytic AML phenotypes . The combined ATP1A1/BCL2L1 ratio improves chemotherapeutic sensitivity prediction .
Regulation of BCL2L1 Expression
The methylation status of CpG sites within the BCL2L1 locus can affect its expression . For example, specific CpG sites at the exon 2 and intron 2 junction of the BCL2L1 locus are tightly correlated and may influence the response to MCL1 inhibitors in pediatric cancers .
Product Specs
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Target Background
- Depletion of miR-34a enhanced endothelial cell growth and inhibited apoptosis in atherosclerosis (AS) by upregulating Bcl-2, suggesting a potential therapeutic target. PMID: 29704100
- BCL-XL promotes stemness and contributes to the aggressiveness of melanoma and glioblastoma. PMID: 29238043
- Treatment with the BH3 domain inhibitor BXI-72 significantly reduced synovial sarcoma cell growth and increased apoptotic signaling in both human and mouse models. PMID: 28851813
- GATA-3 facilitates bone fracture healing by regulating bcl-xL gene expression in conjunction with Runx2. PMID: 29170477
- Necrosis in Mycobacterium tuberculosis-infected macrophages is dependent on Bcl-xl activity. PMID: 28401933
- Mitochondrial Bcl-xL maintains mitochondrial respiratory capacity. Its deficiency leads to oxidative stress, increased glycolytic capacity, and compensatory upregulation of the pentose phosphate pathway. PMID: 28807815
- Proapoptotic proteins BIM and PUMA are not essential for reticulocyte apoptosis induced by BCL-XL loss. PMID: 28682312
- BMP4 promotes neural stem/progenitor cell survival by enhancing Bcl-xL's anti-apoptotic function via BMP4-Smad1/5/8-Id1 signaling in the presence of FGF-2. PMID: 29353044
- Bcl-xL is crucial for the survival of post-mitotic neurons during spinal cord development. PMID: 27665712
- Atherosclerosis-associated endothelial cell apoptosis may be partially caused by Bcl-Xl downregulation via miR-876 upregulation, which suppresses Bcl-Xl mRNA translation. PMID: 28723693
- Bcl-xL drives colorectal tumorigenesis and cancer progression. PMID: 27537525
- Mcl-1 is not essential for apoptosis regulation during large DNA virus infection, while Bcl-XL is important for maintaining the survival of infected cells. PMID: 27537523
- BCL-XL, BCL-2, and MCL-1 differentially regulate B-cell survival throughout development. PMID: 27560714
- Bcl-xL deficiency induced apoptosis in a specific neuronal population, leading to severe neurobehavioral abnormalities. PMID: 27194326
- PUMA loss does not affect BCL-XL-deficient platelet loss, suggesting other BH3-only proteins or alternative mechanisms may regulate platelet apoptosis. PMID: 27221652
- MLF1 is negatively regulated by 14-3-3, preventing Bcl-XL association and inhibiting apoptosis. PMID: 26563351
- Inhibition of BCL-W and BCL-XL selectively eliminates senescent cells. PMID: 27048913
- Valproic acid sensitized TRAIL-resistant papillary thyroid carcinoma cells to apoptosis via Nrf2 and Bcl-xL. PMID: 26721202
- Eosinophil survival is largely regulated by betac chain-induced NF-kappaB activation and subsequent Bcl-x induction. PMID: 25862560
- Beta-cell apoptosis is partially attributable to iPLA2beta-modulated bioactive lipids influencing Bcl-x pre-mRNA 5'SS selection. PMID: 25762722
- Loss of both Bclx alleles significantly inhibited tumorigenesis, while loss of a single Bim allele counteracted this effect. PMID: 24858047
- Only MCL-1, not BCL-XL, is critical for the development and sustained growth of p53-deficient thymic lymphoma. PMID: 25368374
- Plasma cell differentiation proceeds through a Bcl-xL-dependent intermediate, with cell death being C/EBP homologous protein (CHOP)-dependent, linking these events to the unfolded protein response (UPR). PMID: 25023286
- Bcl-xL regulates CD1d-mediated antigen processing and presentation to NKT cells by affecting the late endosomal compartment and CD1d localization. PMID: 25070854
- HAX-1 and BCL-XL have contrasting anti-apoptotic roles in cytokine-dependent bone marrow-derived cells. PMID: 24910348
- The IL-33/ST2 axis promotes mast cell survival via BCLXL. PMID: 24982172
- PP6 regulates apoptosis by modulating Bcl-xL Ser(62) phosphorylation, leading to polyubiquitination and degradation. PMID: 24808369
- A cardiac myocyte signaling cassette (K-Ras, RASSF1A, Mst1) promotes Mst1 activation in response to oxidative stress; activated Mst1 phosphorylates Bcl-xL, antagonizing Bcl-xL-Bax binding, activating Bax, and inducing apoptosis. PMID: 24813943
- The CD28 YMNM motif is critical for T cell proliferation and Bcl-xL expression. PMID: 24639356
- Bcl-xL blocks apoptosis from hypoxia/nutrient loss associated with NK cell-secreted IFN-gamma-mediated angiogenesis inhibition. PMID: 24313893
- Inositol trisphosphate receptors are unique K-Ras4B effectors that antagonize the pro-survival signals of other K-Ras effectors. PMID: 24297914
- Disrupting Bcl-xL:Bax binding rapidly induced apoptosis in neural progenitors and medulloblastoma cells. PMID: 24227720
- Bcl-xL interacts functionally with VDAC1 and -3, but not VDAC2. PMID: 23720737
- Cleavage-resistant Bcl-2 and Bcl-xL are more effective than their wild-type counterparts at inhibiting apoptosis in primary mouse T cells after T cell receptor cross-linking. PMID: 23203923
- In steatotic hepatocytes, the lack of voltage-dependent anion channel phosphorylation is associated with decreased interaction with glycogen synthase kinase 3 and Bcl-XL in mitochondria. PMID: 22814966
- Bcl-xL plays crucial anti-apoptotic roles in the megakaryocytic lineage, preventing lethal or severe spontaneous hemorrhage. PMID: 22790873
- Hesperetin inhibited xenograft growth by downregulating cyclin D1, CDK4, and Bcl-xL, and upregulating p57Kip2 in MCF-7 cells. PMID: 22209285
- Clusterin interacts with Bcl-xL in dying hippocampal CA3 neurons after seizures, while Bcl-xL levels remain constant. PMID: 22197644
- BCL-X is essential for retinal ganglion cell survival during differentiation. PMID: 22836101
- Endoplasmic reticulum-localized Bcl-x(L) affects Ca(2+) homeostasis but does not influence apoptosis unless present in other cellular compartments. PMID: 22573883
- Tanshinone IIA protects neurons from Abeta-induced cytotoxicity, likely via Bcl-xL pathway activation. PMID: 22498308
- Bcl-x(L) and Mcl-1 are essential for megakaryocyte lineage viability. PMID: 22374700
- Targeted Bcl-x deletion significantly impacts the entire macrophage population, modulating macrophage apoptosis resistance. PMID: 22383704
- Noxa and Bcl-xL co-regulate oxidative stress-induced apoptosis. PMID: 22380599
- Increased Bcl-x(L) may reflect impaired adaptation, potentially relevant to myeloproliferative disease mechanisms. PMID: 22086418
- Down syndrome model mice exhibit hippocampal Bcl-X(L) downregulation. PMID: 21684326
- Patients with Lnk/Sh2b3 mutations may exhibit apoptosis resistance in hematopoietic stem cells due to thrombopoietin-mediated Bcl-xL upregulation. PMID: 22101255
- Bcl-xL is crucial for lymphomagenesis in c-Myc overexpressing mice, unlike Bcl-2. PMID: 21998213
- EVI1 directly induces Bcl-xL expression via its zinc finger domains, inhibiting apoptosis. PMID: 21980434
- Hrk deficiency does not significantly reduce apoptosis in the Bcl-x (-/-) embryonic nervous system, indicating other BH3-only molecules may regulate BAX activation in immature neurons. PMID: 22043021
