Mcl_1 monocl Ab; human (clone 22)
- Known as:
- Mcl_1 monocl Antibody; H. sapiens (clonality 22)
- Catalog number:
- ASAAAM-241E
- Product Quantity:
- 100 µg
- Category:
- -
- Supplier:
- Other suppliers
- Gene target:
- Mcl_1 monocl ; human (clone 22)
Related genes to: Mcl_1 monocl Ab; human (clone 22)
- 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: Mcl_1 monocl Ab; human (clone 22)
Related articles to: Mcl_1 monocl Ab; human (clone 22)
- Protein arginine methyltransferase 5 (PRMT5), a type II arginine methyltransferase, is overexpressed in several aggressive B-cell malignancies and facilitates cancer cell proliferation. JNJ-64619178, a selective small-molecule inhibitor targeting PRMT5, has previously shown promising preclinical activity across a range of hematological malignancies; however, the clinical activity of JNJ-64619178 monotherapy is limited despite strong target engagement. Therefore, we sought to identify rational combination partners for JNJ-64619178 to achieve improved activity in B-cell malignancies. Using dynamic Bcl-2 homology 3 (BH3) profiling, a functional assay to evaluate the net increase in proapoptotic signaling in response to drugs, we found that JNJ-64619178 increased overall proximity to apoptotic cell death (mitochondrial apoptotic priming) and dependence on B-cell leukemia/lymphoma (BCL)-2 for survival (BCL-2 dependence), particularly in diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) cell lines. In other B-cell non-Hodgkin lymphoma (B-NHL) cell lines that are primarily MCL-1 dependent and less BCL-2 dependent, JNJ-64619178 increased mitochondrial apoptotic priming without shifting anti-apoptotic dependence from MCL-1 to BCL-2. Co-targeting PRMT5 and BCL-2 synergistically induced apoptosis in DLBCL and MCL cell lines that displayed at least partial BCL-2 dependence at baseline, but not in less BCL-2-dependent B-NHL cell lines. Interestingly, JNJ-64619178 upregulated death receptor 4 (DR4) and death receptor 5 (DR5) expression on the cell membrane of B-NHL cell lines, thereby sensitizing them, including the less BCL-2-dependent cell lines, to recombinant TRAIL-induced extrinsic apoptotic cell death. These findings highlight a role of PRMT5 in regulating both intrinsic and extrinsic apoptosis and suggest potential combination partners with PRMT5 inhibitors for potential clinical application in B-NHL. - Source: PubMed
Publication date: 2026/05/16
Zhu FenWang JingRyan Christine EHackett LiamZhang JeremyChamberlain StephanieUng JohnsonChong Stephen J FDavids Matthew S - Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide, with obesity recognized as a major modifiable risk factor. Obesity-associated CRC is characterized by systemic low-grade inflammation, altered lipid metabolism, and gut microbial dysbiosis, all of which converge to create a pro-inflammatory niche. Emerging evidence implicates murine miR-101a/b, an ortholog of the human miR-101 family, as a key molecular mediator linking metabolic dysfunction, promoting inflammation, endotoxemia, and affecting epithelial homeostasis. Traditionally, the miR-101 family is considered a tumor suppressor by repressing oncogenes such as EZH2, MCL-1, and COX-2; miR-101a appears to exhibit a paradoxical microenvironment-modulating role in obese colon. Recent studies demonstrate that elevated dietary and microbiota-derived ethanolamine induces miR-101a overexpression in colonic epithelial cells. Mechanistically, miR-101a directly destabilizes the mRNA encoding the tight junction protein (ZO-1; TJP1), thereby impairing epithelial barrier integrity, increasing intestinal permeability, and promoting chronic inflammation. The chronic inflammation promotes epithelial proliferation, generates mutagenic reactive oxygen species, and activates pro-survival pathways such as STAT3 and AKT, collectively contributing to a tumor-permissive microenvironment that may support adenoma initiation and progression. The resulting chronic inflammatory milieu promotes epithelial stress, proliferative signaling, and accumulation of DNA damage, contributing to conditions that favor colorectal carcinogenesis. Importantly, this ethanolamine-miR-101a axis represents a novel mechanistic link between diet, microbiota, and cancer biology. Translationally, miR-101a holds promise as a biomarker of early barrier dysfunction and CRC risk, as detectable in tissue, serum, or fecal samples. Furthermore, microbiome-targeted interventions, dietary modifications, or direct inhibition of miR-101a may offer innovative therapeutic strategies. Collectively, these findings support the development of precision microbiome-miRNA-based approaches and highlight the importance of context-dependent miRNA regulation in obesity-associated CRC. - Source: PubMed
Publication date: 2026/06/12
Mishra Sidharth PrasadJacobson RichardWang BoPrajapati SantoshSanberg PaulBrechot ChristianJain ShaliniYadav Hariom - De novo purine synthesis is required to maintain tumor growth; however, its impact on therapy resistance remains unclear. Here, through a dynamic BH3-priming-based CRISPR screen, we found that deletion of ADSS2, which encodes the adenylosuccinate synthase 2 enzyme essential for adenosine monophosphate (AMP) synthesis, re-sensitizes drug-resistant acute myeloid leukemia cells to venetoclax and a myeloid cell leukemia-1 (MCL1) inhibitor. Single-cell sequencing analysis of patient-derived xenograft samples revealed a positive association of high ADSS2 activity in TP53-mutant cells with poor responsiveness to venetoclax. We developed an ADSS2 antagonist, which synergized with BH3 mimetics to promote apoptosis in preclinical models. Mechanistically, sensitization mediated by ADSS2 targeting correlated with downregulated AMP-activated protein kinase activity, which in resistant cells promotes mitophagy to eliminate damaged mitochondria after BH3 mimetic treatment. These data show that AMP synthesis promotes BH3 mimetic resistance and that combining ADSS2 targeting with BH3 mimetics represents a promising anti-cancer approach. - Source: PubMed
Publication date: 2026/06/26
He XinZhang LeiLi YangLiu Song-BaiLi ZhengDong HaojieBaker Genevieve ENguyen Le Xuan TruongChen WeiWang JinhuiJia ZhilianLu XiyuanLin Yi-ChunHu ZunsongYadav Umesh PrasadLiu MengZhang LianjunChen ZhenhuaWu XiweiChen JianjunChen Chun-WeiTiziani StefanoHu WeidongKuo Ya-HueiXue Sheng-LiZhang YongLi MinZhu YaoqiuMarcucci GuidoGu ZhaohuiPerry J Jefferson PLuo Yun LynaLi Ling - There are currently no effective targeted therapies for BRAF-mutant metastatic melanoma patients with acquired resistance to approved BRAF and MEK inhibitors (BRAFi and MEKi), and very few ongoing clinical trials. Anti-apoptotic BCL2 family proteins promote de novo resistance to several therapies, including single-agent BRAFi in BRAF-mutant melanomas. In this study, in vivo testing of a large collection of patient-derived xenograft (PDX) models from melanoma patients with acquired resistance to BRAFi or BRAFi+MEKi shows that combining BCL2 inhibitors (BCL2i; navitoclax or venetoclax) with BRAFi+MEKi induces tumor regressions in a subset of these PDXs. High basal BCL2 predicts response whereas high basal MCL1 predicts resistance to this strategy. MCL1 overexpression studies functionally validate its role in resistance. Further, combining BRAFi+MEKi with an MCL1 inhibitor (MCL1i) counteracts resistance and interestingly decreases MCL1i-associated markers of cardiotoxicity. Together these studies identify potential personalized strategies to improve outcomes in this challenging patient population. - Source: PubMed
Publication date: 2026/06/26
Y N Vashisht Gopalde Groot EvelynLoftin KaleyKnighton BarbaraLedesma DeboraHudgens CourtneyShamsutdinova DianaAli MehboobJu ZhenlinXiao MinKannan ToshithaFontenot GregoryNakazawa Michael SThomas MonzyWani KhalidaStephan CliffordAung Phyu PKwong Lawrence NRoszik JanosAkbani RehanKossenkov AndrewRebecca Vito WSullivan Ryan JHerlyn MeenhardDavies Michael A - Liver ischemia-reperfusion injury (LIRI), a significant complication following liver transplantation and surgical procedures, remains inadequately addressed due to the limited therapeutic options available. This study aims to elucidate the pivotal regulators underlying the maladaptive immune responses and mitochondrial dysfunction associated with LIRI. By integrating multiple microarray datasets (GSE12720, GSE112713, GSE23649, and GSE151648) and single-cell RNA sequencing (scRNA-seq) data (GSE171539), we employed weighted gene co-expression network analysis (WGCNA) alongside four machine learning algorithms (SVM, LASSO, RF, and XGBoost) to identify hub genes. Our analyzes highlighted MCL1 as a critical hub gene linked to mitochondrial function, exhibiting significantly elevated expression levels in LIRI, coupled with strong diagnostic accuracy. Further single-cell analysis revealed MCL1's specific enrichment in endothelial cells (ECs) and macrophages (MCs), along with the identification of a novel macrophage subset (CSF1RIL-1BMCL1) characterized by a dual pro-inflammatory and pro-survival phenotype. This finding suggests enhanced intercellular crosstalk involving key pathways such as NF-κB, apoptosis, and cytokine signaling, while in silico knockout of MCL1 markedly disrupted immune-related gene networks. Validation studies confirmed MCL1 upregulation and the presence of the macrophage subset in a murine LIRI model. In conclusion, our findings position MCL1 as a vital regulator linking immune inflammation and mitochondrial dysfunction in LIRI, proposing it as a promising diagnostic biomarker and therapeutic target for managing this condition, though its optimal therapeutic direction requires further investigation. - Source: PubMed
Chen XianxiangXing SiyiBao YuntaoYuan GuandouGao WeiWang YunchuanLiu MingjiangZeng YonglianLi ZeyuanHe SongqingXiao Fang