Ask about this productRelated genes to: Bcl-G antibody
- Gene:
- BCL2 NIH gene
- Name:
- BCL2 apoptosis regulator
- Previous symbol:
- -
- Synonyms:
- Bcl-2, PPP1R50
- Chromosome:
- 18q21.33
- Locus Type:
- gene with protein product
- Date approved:
- 2001-06-22
- Date modifiied:
- 2019-04-23
- Gene:
- BCL2L1 NIH gene
- Name:
- BCL2 like 1
- Previous symbol:
- -
- Synonyms:
- BCLX, BCL2L, Bcl-X, bcl-xL, bcl-xS, PPP1R52
- Chromosome:
- 20q11.21
- Locus Type:
- gene with protein product
- Date approved:
- 1997-10-30
- Date modifiied:
- 2016-01-13
- Gene:
- BCL9L NIH gene
- Name:
- BCL9 like
- Previous symbol:
- -
- Synonyms:
- DLNB11, B9L, Bcl9-2
- Chromosome:
- 11q23.3
- Locus Type:
- gene with protein product
- Date approved:
- 2003-12-09
- Date modifiied:
- 2018-11-16
Related products to: Bcl-G antibody
Related articles to: Bcl-G antibody
- Intrinsic apoptosis is a form of cell death which is activated, executed, and inhibited by the Bcl-2 protein family. The structural basis of the inhibition mechanisms remains elusive. Here, we characterize the ensemble structural model of the inhibitory Bcl-xL/tBid complex at the mitochondrial membrane by probing interresidue distances and dynamic solvent accessibilities complemented by integrative modeling and molecular dynamics simulations. We show that Bcl-xL and tBid form a heterodimer anchored to the membrane by the C-terminal helix of Bcl-xL. The BH3 domain of tBid is wedged between the exposed hydrophobic groove of Bcl-xL and the membrane headgroups, while tBid's C-terminal helices remain dynamically engaged with the bilayer. This dynamic architecture sheds light on the mechanism of indirect inhibition of apoptosis. - Source: PubMed
Publication date: 2026/05/11
Elsner ChristinaHanke AntonVadas OscarGervasio Francesco LuigiBordignon Enrica - Chronic infection with hepatitis B virus (HBV) remains a global health issue, leading to liver diseases such as chronic hepatitis B, cirrhosis, and hepatocellular carcinoma. The HBV X protein (HBx) promotes viral replication and disease progression by interacting with various host proteins. One of its functions involves binding to microtubule-associated protein 1 light chain 3B (LC3B), which mediates selective autophagy and facilitates the removal of the immune-related protein TNFRSF10B (tumor necrosis factor receptor superfamily 10B). However, even the mechanism by which HBx interacts with LC3B remained unclear. In this study, we focused on the HBx-LC3B interaction as a first step and identified a conserved LC3-interacting region motif (Trp120-X-X-Leu123) within the Bcl-2 homology 3 (BH3)-like domain of HBx that directly binds to LC3B. This interaction was characterized using isothermal titration calorimetry and nuclear magnetic resonance (NMR) spectroscopy. We present the first NMR structure of LC3B in complex with the HBx BH3-like peptide, revealing that it adopts an extended conformation upon binding and that Trp120 and Leu123 are essential for LC3B recognition. Notably, the same portion forms an α-helix when binding to B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma extra-large (Bcl-x), suggesting that HBx uses different conformations to interact with distinct targets. This structural plasticity may underlie the multifunctional roles of HBx. - Source: PubMed
Publication date: 2026/05/06
Kusunoki HidekiTanaka ToshiyukiMizukami TakuoWakamatsu KaoriNagata Takashi - Mutations in the RAS gene family (NRAS, KRAS) are critical drivers of late-stage acute myeloid leukemia (AML) progression. They are frequently detected in relapsed/refractory AML and AML transformed from myelodysplastic syndrome (MDS). Occurring as late-stage genetic events, RAS mutations synergize with early drivers to promote leukemogenesis. While mutually exclusive with FLT3-ITD mutations, they coexist with KIT, RUNX1, CEBPA mutations and MLL rearrangements. Granulocyte-monocyte progenitors (GMPs) serve as the cellular origin for RAS-mutant leukemia stem cells (LSCs). Ultimately, RAS mutations drive monocytic differentiation of LSCs and venetoclax (VEN) resistance through BCL-2 family rewiring. Beyond AML, they are hallmark genetic lesions in juvenile myelomonocytic leukemia (JMML) and present in 15%-20% of pediatric acute lymphoblastic leukemia (ALL) cases. Here, we propose a comprehensive pathogenic model and targeted therapeutic framework focusing on RAS, MCL-1, BCL2L1 to overcome drug resistance and improve patient outcomes. - Source: PubMed
Publication date: 2026/04/11
Jiang CongfaWang HangxuanZhao JiaxinXu YuweiDuan Shiwei - The degradation of plastic waste leads to the release of numerous chemical additives, including phthalate plasticizers, which have been implicated in the pathogenesis of metabolic disorders. Di (2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer whose primary metabolite, mono (2-ethyl-5-carboxypentyl) phthalate (MECPP), has been associated with multiple metabolic diseases. In this study, we applied an integrated approach combining network toxicology and molecular docking to systematically investigate the potential mechanistic role of MECPP in metabolic dysregulation. Our strategy included multi-platform target prediction, disease gene association analysis, functional enrichment, protein-protein interaction network construction, and molecular docking analysis. The results suggested that MECPP may be associated with six common core targets, including BCL2, BCL2L1, MAPK14, MMP2, MMP9, and TNFRSF1A, which are mainly involved in apoptosis, inflammatory regulation, and extracellular matrix remodeling. Pathway enrichment analysis further indicated the potential involvement of several disease-overlapping pathways, including insulin resistance, neuroactive ligand-receptor interaction, efferocytosis, advanced glycation end product-receptor for advanced glycation end product (AGE-RAGE) signaling, phospholipase D signaling, and renin secretion. Overall, these findings suggest that MECPP may contribute to metabolic dysregulation through overlapping molecular mechanisms across multiple diseases. This study provides a computational basis for future experimental validation and environmental risk assessment. - Source: PubMed
Publication date: 2026/04/16
Qiu JiaqiCheng ChangJiang BiaoYang DiqiPeng Hui - Breast cancer is a profound cause of mortality among women globally. Similar to BH3 mimetics, targeting the antiapoptotic Bcl-xL:Beclin1 protein complex is crucial to inducing apoptosis and autophagy, thereby suppressing tumor progression in breast cancer cells. This study aims to synthesize and evaluate a series of imidazopyridine-tethered pyrazoline drug prejudice-scaffold derivatives (5a-5l) as Beclin-1 mimetics that induce apoptosis and autophagy and mainly for their potential anticancer activity, focusing on the most potent compound 5c. The primary goal is to assess its ability of compound 5c to inhibit Bcl-xL:Beclin-1 interaction, thereby inducing a protective autophagic response subsequently to assess apoptosis to suppress breast cancer cell proliferation. Molecular docking studies were conducted to evaluate the binding affinity of compound 5c with Bcl-xL, and the interactions were visualized through a three-dimensional interaction map, highlighting key stabilizing interactions. Cytotoxic effects of compound 5c on MCF-7 breast cancer cells were assessed using alamarblue assay. To investigate the antiproliferative potential, colony formation, and wound healing assays were performed at varying concentrations. Apoptotic induction was analyzed through Western blotting for key proteins (BAX, Bcl-xL, Bcl-2), caspase-3/7 activation, and AnnexinV/PI assay using flow cytometry. Additionally, autophagy was examined by monitoring LC3B-I to LC3B-II conversion, Beclin-1 upregulation, and lysosomal activity using LysoTrackerRed staining. The involvement of compound 5c in autophagic flux was further confirmed by quantifying LC3-II accumulation in the presence of an autophagy inhibitor chloroquine (CQ), and then the effect of 5c-induced cell viability and apoptosis were evaluated and caspase-3/7 activity, respectively, during autophagy inhibition condition in MCF-7 cell line. A strong binding interaction of compound 5c with the hydrophobic groove of Bcl-xL demonstrated its potential as an effective Bcl-xL inhibitor. Compound 5c significantly reduced MCF-7 cell viability in a dose-dependent manner (IC50: 9.7 μM). The inhibitory effect of compound 5c on cancer cell proliferation and migration was observed. Treatment with compound 5c induced dose-dependent apoptosis in MCF-7 cells, as confirmed by Annexin V/PI using flow cytometric analysis after 72 h of exposure. A significant decrease in viable cells accompanied by an increase in apoptotic cell populations was observed with increasing concentrations of 5c. Upregulated BAX expression and downregulation in Bcl-xL and Bcl-2 expression levels indicated apoptosis induction. Caspase-3/7 activation further confirmed apoptotic cell death. Autophagy assessment revealed enhanced LC3B-II accumulation, Beclin-1 upregulation, and reduced p62 levels, suggesting modulation of autophagy. CQ treatment further increased LC3-II levels, indicating compound 5c-mediated autophagic flux induction and a significant reduction in cell viability and increased caspase 3/7 activity, confirming modultion of autophagy-dependent apoptosis by 5c. Similar to BH3 mimetic, compound 5c emerges as a promising small-molecule inhibitor targeting the Bcl-xL:Beclin-1 complex, which effectively induces apoptosis by modulating protective autophagy in breast cancer cells. Its dual mechanism of action highlights its potential as a novel therapeutic candidate for breast cancer treatment. - Source: PubMed
Shivakumar RashmiBeeraka Narasimha MOsmani Riyaz Ali MRavi Bhoomika BYadhav Monisha H SNagaraju DileepBhol Chandra SekharNagalakshmi AllakaAhn Kwang SeokNikolenko Vladimir NChinnathambi ArunachalamBender AndreasBasappa Basappa