Anti_human Mcl_1 rabbit polyclonal
- Known as:
- Anti_human Mcl_1 host: rabbit pab
- Catalog number:
- ASA905-460
- Product Quantity:
- 1 mL
- Category:
- -
- Supplier:
- Other suppliers
- Gene target:
- Anti_human Mcl_1 rabbit polyclonal
Related genes to: Anti_human Mcl_1 rabbit polyclonal
- Gene:
- MCL1 NIH gene
- Name:
- MCL1 apoptosis regulator, BCL2 family member
- Previous symbol:
- -
- Synonyms:
- BCL2L3, Mcl-1
- Chromosome:
- 1q21.2
- Locus Type:
- gene with protein product
- Date approved:
- 1993-11-09
- Date modifiied:
- 2019-01-25
Related products to: Anti_human Mcl_1 rabbit polyclonal
Related articles to: Anti_human Mcl_1 rabbit polyclonal
- Current diagnostics for ischemic stroke (IS) lack timeliness and accessibility, highlighting the need for novel molecular diagnostic models. Three gene expression datasets (GSE16561, GSE22255 and GSE58294), encompassing both IS patients and healthy control subjects, were retrieved from a public database. The mitochondrial dysfunction genes retrieve from the intersection of the GeneCards and MitoCarta3.0 databases. The limma and WGCNA package were used to obtain the genes related to IS. Feature genes were screened using LASSO, RF, SVM, and diagnostic models were constructed using NeighborMethod, NeuralNet, and BayesMethod. 3548 differentially expressed genes (DEGs) (1538 upregulated, 2010 downregulated) were identified in IS patients when compared to controls. WGCNA analysis yielded 10 IS-related modules containing 1643 genes. The intersection of DEGs, module genes, and mitochondrial dysfunction genes yielded 100 mitochondrial dysfunction genes associated with IS. These genes collectively regulate biological processes like mitochondrial ATP synthesis coupled electron transport and respiratory electron transport chain, and participate in IS-associated signaling pathways such as reactive oxygen species and oxidative phosphorylation. Further machine learning methods identified 4 feature genes, including MCL1, MRPL46, MTX3 and RNASEH1. These four genes exhibited robust diagnostic potential in the merged dataset (all AUC > 0.7). The machine learning models achieved AUC values of 0.814 (NeighborMethod), 0.852 (NeuralNet), and 0.842 (BayesMethod). External validation using an independent cohort confirmed that all models maintained high diagnostic accuracy (AUC range: 0.730-0.783). This study established a multi-gene diagnostic model for IS, identifying novel molecular biomarkers to improve the timeliness and accessibility of IS diagnosis. - Source: PubMed
Publication date: 2026/05/02
Wu DandanHuang XiaolanLi JieMo DingminLan WeiweiSong ZihanSu LiLong JianxiongYang Jialei - Approximately 85% of all lung cancer cases are classified as non-small cell lung cancer (NSCLC). Given its poor prognosis and resistance to radiotherapy and chemotherapy, there is an urgent need to elucidate its molecular mechanisms to develop novel and more effective therapeutic strategies. In prior research, we identified nobiletin from a compound library and confirmed it as a novel natural BH3 mimetic. Nobiletin synergized with vorinostat to induce autophagy and apoptosis in small-cell lung cancer. In the current study, we further demonstrate that nobiletin, either alone or in combination with vorinostat, exerts inhibitory effects on NSCLC. Specifically, the combination of nobiletin and vorinostat suppressed the proliferation of NSCLC A549 cells. Nobiletin, used alone or with vorinostat, induced apoptosis in A549 cells by mimicking BH3-only proteins, which included down-regulating anti-apoptotic proteins such as B-cell lymphoma-2 (BCL-2) and MCL-1, up-regulating apoptosis-related proteins Cleaved-Caspase-3 and Cleaved-PARP, and increasing BH3-only protein expression. Nobiletin binding to BCL-2 facilitated the dissociation of the Beclin-1/BCL-2 complex, thereby elevating levels of free Beclin-1. Furthermore, the combination of nobiletin and vorinostat enhanced the expression of LC3A/BII and forkhead box O1 (FOXO1), ultimately inducing autophagy in A549 cells. Eukaryotic transcriptome sequencing revealed that the combination treatment primarily inhibits tumor cell proliferation by modulating TRKC protein expression and suppressing phosphorylation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. Therefore, our results indicate that nobiletin, a natural BH3 mimetic, synergizes with vorinostat to regulate both apoptosis and autophagy in NSCLC. - Source: PubMed
Wang YuanruFan FangYang XueLi YuqianLi LuyaoLei QiqiXiang LiuyanZhang XiaoqianCao YajunLi Xuejun - SETD2 is frequently mutated or deleted in clear cell renal cell carcinoma (ccRCC). Loss of SETD2 could create synthetic lethal dependencies that confer therapeutic vulnerabilities. Here, we demonstrated that SETD2 deficiency promotes cytoplasmic mitochondrial DNA (mtDNA) leakage, leading to basal activation of cGAS-STING inflammatory signaling and increased apoptotic priming. This inflammatory state upregulated the BH3-only protein NOXA, constrained MCL-1 function, and enforced a synthetic lethal dependency on the anti-apoptotic protein BCL-xL. Pharmacological inhibition of BCL-xL further amplified cGAS-STING signaling in SETD2-deficient cells through sublethal mitochondrial outer membrane permeabilization, resulting in increased mtDNA release and robust NOXA induction. Elevated NOXA neutralized the compensatory MCL-1-mediated survival signaling, triggering apoptosis. In contrast, SETD2 proficient ccRCC cells exhibited minimal cGAS-STING activation and failed to induce NOXA following BCL-xL inhibition, rendering them resistant. Genetic ablation of cGAS, STING, IRF3, or NOXA rescued sensitivity to BCL-xL inhibition, confirming that mtDNA-driven innate immune signaling is required for this dependency. In vivo, BCL-xL inhibition suppressed tumor growth and prolonged survival in SETD2-deficient xenograft models. Collectively, these findings establish a mechanistic link between SETD2 loss, mtDNA-driven innate immune activation, and enforced BCL-xL dependence in ccRCC, revealing a therapeutically targetable vulnerability in SETD2-deficient tumors. - Source: PubMed
Publication date: 2026/04/30
Uprety AnushaJudd ChandlerVillella Emily DKeller RebeccaWagner RyanRobertson Keith DRodriguez-Blanco JezabelBarnoud ThibautMason Frank MHo Thai Hde Cubas Aguirre A - Resistance to Bruton tyrosine kinase inhibitors (BTKi) is inevitable in mantle cell lymphoma (MCL). Cyclin-dependent kinase-9 (CDK9), a key regulator of oncogenic transcription, is a promising therapeutic target. Here we studied a selective CDK9 inhibitor, AZD4573, in MCL. Treatment with AZD4573 thwarted growth of both parental and ibrutinib-resistant MCL cell lines and primary MCL cells and downregulated expression of MYC and MCL1. However, CDK9 inhibition enhanced basal and maximal oxygen consumption rate, as well as increased production of ATP and reactive oxygen species in ibrutinib-resistant cell lines and primary MCL cells. While treatment with AZD4573 led to modest prolongation of survival in an ibrutinib-resistant MCL PDX mouse model, accompanied by downregulation of TNF/NF-B and mTORC1 signaling pathways in murine splenocytes, OxPhos was upregulated suggesting tumor metabolic reprogramming. Single-cell RNA Sequencing analysis of PBMCs from patients treated with AZD4573 on a clinical trial demonstrated sustained downregulation of MYC targets and OxPhos in malignant B-cells from a responding patient with MCL. Conversely, two refractory patients exhibited upregulation of MYC targets and OxPhos in PBMCs. OxPhos inhibitor IACS-010759 demonstrated synergy with AZD4573 in vitro. Thus, CDK9 inhibition exhibits activity in ibrutinib-resistant MCL and can be further enhanced by co-targeting of OxPhos. - Source: PubMed
Publication date: 2026/04/28
Roleder CarlyZhao XiaofanLam ViShen HaifengDominguez Edward CChen CanpingRodriguez-Rodriguez SoniaWang LiliPhillips TycelXia ZhengDanilov Alexey V - Venetoclax, a chemotherapeutic agent for hematologic malignancies, faces resistance due to Myeloid Cell Leukemia-1 (MCL-1) upregulation. AMG-176, an MCL-1 inhibitor, shows promise as a therapeutic target in these malignancies. However, the serum metabolic profile following AMG-176 intervention in chronic lymphocytic leukemia (CLL) remains unexplored. This study aims to elucidate potential biomarkers and mechanisms of AMG-176 intervention in CLL. Peripheral blood mononuclear cells (PBMCs) isolated from five CLL patients were treated with varying doses of AMG-176. The IC50 value was determined using the CCK8 assay. After 24-hour intervention, cell supernatants underwent untargeted metabolomics analysis via Liquid Chromatography-Mass Spectrometry (LC-MS). Distinct metabolic profiles emerged between control, low-dose, and high-dose AMG-176 groups. Of 1,934 identified metabolites across 23 classes, six differential metabolites (L-Glutamine, L-Phenylalanine, Xanthosine, Inosine, Guanosine, and 2'-Deoxyadenosine) were enriched in multiple pathways. L-Glutamine and L-Phenylalanine, notably associated with leukemia, showed significant concentration-dependent changes with AMG-176 intervention. Key enriched pathways included metabolic pathways, ABC transporters, and amino acid biosynthesis. L-Glutamine and L-Phenylalanine emerge as potential biomarkers for AMG-176 intervention in CLL, warranting further validation in larger studies. This metabolomics-based pilot study provided a reference for the treatment of CLL and the application of AMG-176. - Source: PubMed
Publication date: 2025/06/10
Yi XueXing DonghuiZhai YixinGuan JunWang LanlanLi QinZhao Zhigang