Ask about this productRelated genes to: BBC3 Blocking Peptide
- Gene:
- BBC3 NIH gene
- Name:
- BCL2 binding component 3
- Previous symbol:
- -
- Synonyms:
- JFY1, PUMA
- Chromosome:
- 19q13.32
- Locus Type:
- gene with protein product
- Date approved:
- 2002-07-22
- Date modifiied:
- 2017-03-13
Related products to: BBC3 Blocking Peptide
Related articles to: BBC3 Blocking Peptide
- While venetoclax-based combinations have shown promising results in acute myeloid leukemia (AML), the remission duration is generally short, warranting strategies to further improve efficacy and overcome resistance. Here, we show that the natural quassinoid brusatol induces cell-cycle arrest and apoptosis in multiple AML cell lines while enhancing venetoclax efficacy irrespective of inherent or acquired resistance. Mechanistically, brusatol increased p53 protein expression, leading to upregulation of its target genes/proteins, including CDKN1A (p21) and BBC3 (PUMA). Genetic deletion of TP53 attenuated brusatol-induced apoptosis and its synergy with venetoclax, supporting p53 activation as a central mechanism underlying the anti-leukemia response. Furthermore, the combination synergistically decreased mitochondrial membrane potential and respiratory activity, causing accumulation of reactive oxygen species in AML cells. Although brusatol and venetoclax exhibited limited effects individually, their combination markedly reduced leukemia burden and significantly prolonged survival in three independent cell line-derived xenograft models, including venetoclax-resistant and -refractory models. Notably, brusatol increased normal leukocyte and platelet counts while reducing leukemic infiltration in both bone marrow and extramedullary sites. These findings provide mechanistic insight into the synergistic effects of the brusatol-venetoclax combination, supporting further evaluation of this therapeutic strategy in myeloid leukemias. - Source: PubMed
Publication date: 2026/05/21
Kawaguchi Shin-IchiroSato KazuyaIzawa JunkoTakayama NorihitoHayakawa HirokoSuzaki KenGoyama SusumuKato ChiyokoSakashita EijiTominaga KaoruEndo HitoshiKanda Yoshinobu - Point mutations in p53 favour tumour aggressivity, particularly in gastric cancer (GC), and offer a target for small molecule-based anticancer treatments. This study focused on the p53-Y220C mutation, which causes p53 misfolding due to thermal instability associated with the creation of a pocket that may accommodate small molecules. This mutation also creates an additional free cysteine thiol group that may react with Michael acceptors. Using an integrated and approach, four compounds (AG1, AG2, AG3, and RK349) were screened for potential reactivation of p53-Y220C in GC cells. AG3, a compound with zinc chelation and Michael acceptor properties, was found to induce p53 target gene expression via p53-dependent and -independent pathways. AG3 limited reactive oxygen species production, reducing toxicity to healthy cells. Furthermore, AG3 induced p53-dependent cytotoxicity and enhanced chemotherapy response. This study presents a novel compound with p53-Y220C reactivation potential, highlighting its promise for further development. - Source: PubMed
Publication date: 2026/05/21
Nannini SimonSieffert CélineMcGown AndrewGao Xin-YueJarvis AmandaKostakis Georges EGalvacsi AntalKallay CsillaMoraru RuxandraBaud Matthias GMandel SebastianBalourdas Dimitros-IliasJoerger Andreas COrvain ChristophePeschard SimonNion AudreyMellitzer GeorgLottiaux SophieSpencer JohnGross IsabelleGaiddon Christian - The innate immune signaling pathway cGAS-STING plays an important role in the recognition of cytosolic nucleic acids and the induction of the interferon-dependent antiviral response. Despite the significant research interest in this cascade in the context of immune system function, the mechanisms regulating cGAS-STING signaling and the switch between its pro-inflammatory and pro-apoptotic effects remain largely underexplored. According to publicly available RNA-seq data and microarray analyses, SETD7 lysine methyltransferase participates in interferon signaling in cancer cells. This study aims to elucidate the role of SETD7 in the regulation of the STING-dependent immune response in human lung adenocarcinoma (LUAD) cells. For this purpose, we developed a reproducible and cost-effective method for inducing the STING cascade by transfecting cells with salmon sperm DNA (sspDNA). We demonstrated that sspDNA efficiently induces phosphorylation of the key components of the STING-TBK1-IRF3 signaling pathway and activates the expression of interferons and pro-inflammatory cytokines. Using this approach, we further demonstrated that SETD7 is involved in the regulation of the IRF3-dependent transcriptional program. Suppression of SETD7 was associated with changes in the expression of genes related to innate immune response and apoptosis, including increased levels of , , , (PUMA), and . Furthermore, attenuation of SETD7 expression reduced the lentiviral transduction efficacy in H1299 cells. These results suggest that SETD7 may play a role in regulating the switch in STING signaling between pro-inflammatory and pro-apoptotic responses in LUAD cells. - Source: PubMed
Publication date: 2026/04/30
Nevzorov Ivan AKorableva PolinaShuvalov OlegParfenyev SergeyBarlev Nickolai ADaks Alexandra - Hyperglycemia exacerbates cerebral ischemia/reperfusion (I/R) injury, apoptosis pathways playing a key role. Sodium selenite (SE) exhibits neuroprotective effects, however, whether the Fas/FasL/PUMA pathway is involved in this neuroprotective effects remains unclear. For help to make this clear, hyperglycemic-aggravated cerebral I/R models (SD rats) and in vitro high-glucose oxygen deprivation/reoxygenation (OD/R) models (HT22 cells) were applied in this study. This study showed that the cerebral infarct volume and neuronal damages in the hyperglycemic I/R rat indeed were alleviated by the selenite treatment. And the lost neurological functions were improved by selenite treatment also. In the HT22 cells, the SE treatment enhanced viability and reduced reactive oxygen species (ROS) accumulation. Mechanistically, this study showed that the SE treatment downregulated the expressions of Fas, FasL, p-NF-κB, PUMA, Cleaved Caspase-3, and Cytochrome c, while increased the Bcl-2/Bax expression ratio. The SE's anti-apoptotic effects were potentiated by PUMA knockdown or autophagy inhibitor 3-MA co-treatment. These findings confirm that SE alleviates hyperglycemia-exacerbated cerebral I/R injury by inhibiting the Fas/FasL/PUMA apoptotic pathway, providing a therapeutic strategy for hyperglycemia ischemic stroke. CONCLUSION: Sodium selenite alleviates hyperglycemia-exacerbated cerebral I/R injury by modulating the Fas/FasL/PUMA signaling pathway. SIGNIFICANCE STATEMENT: The finding that sodium selenite alleviates hyperglycemia - exacerbated cerebral I/R injury by modulating the Fas/FasL/PUMA signaling pathway advances knowledge in neuroscience by revealing a novel mechanism through which a compound can mitigate the harmful effects of hyperglycemia on cerebral I/R injury, and it deepens our understanding of how apoptotic pathways in the nervous system can be regulated to protect against such injuries. - Source: PubMed
Publication date: 2026/04/26
Yang LanDing FengYin XidaZhao ShuaiChang YueZhang JingwenHuang NingboWang WenjunJing Li - Microplastics are emerging contaminants that pose health risks. They can cause hepatic lipid interventions, but the underlying mechanisms require investigation. This study assessed the retention of polypropylene microplastics in mouse liver and determined the intercorrelations between hepatic lipid fluctuations and transcriptomic changes. Microplastic-induced liver dysfunction was confirmed by the variations of transamination, cholesterol metabolism, biotransformation, and redox state. Chronic high-dose treatment induced distinct pathological changes, including regional fibrotic remodeling and ultrastructural mitochondrial abnormalities. Raman biospectra of liver slice proposed vital peaks of 1060, 1132, 1168, 1340, 1446, 1618, and 1670 cm, representing the liver biomolecule landscapes. Transcriptomic changes were mainly involved in mRNA transcription, multicellular organism development, various stimuli response, cell differentiation, and lipid metabolic process. Microplastic exposure dosage exerted more profound effects than exposure duration on gene expressions of oxidation-reduction process, signal transduction, and lipid metabolism. WGCNA analysis proposed 47 hub genes involved gene expression orchestration, cell fate monitor, and mitochondria translation modulation. Nine differentially expressed genes associated with lipid biomarkers were related to mitochondria transcription ( and ), cell differentiation , and ), lipid catabolism ( and ) and tRNA methyltransferase (), and Raman peak at 1670 cm intimately connected with aggregated forms of protein. Our findings suggested that polypropylene microplastics could change the liver molecular landscape and induce lipid metabolism disorders and transcriptomic changes in mitochondrial protein translation and expression regulation, highlighting their significant consequences in nutrient and energy imbalance. - Source: PubMed
Publication date: 2025/10/29
Wang MiaoWang JingSun XinglinZhang KenaGao JingXu XiaoyingWu JiaruiTao FangfangZhang DayiLiu Mingying