MKK4 (Constitutively Active) Recombinant Adenovirus
- Known as:
- MKK4 (Constitutively Active) Recombinant Adenovirus
- Catalog number:
- ADV-161
- Product Quantity:
- 50
- Category:
- -
- Supplier:
- Cell Biolabs
- Gene target:
- MKK4 (Constitutively Active) Recombinant Adenovirus
Related genes to: MKK4 (Constitutively Active) Recombinant Adenovirus
- Gene:
- MAP2K4 NIH gene
- Name:
- mitogen-activated protein kinase kinase 4
- Previous symbol:
- SERK1
- Synonyms:
- MEK4, JNKK1, PRKMK4, MKK4
- Chromosome:
- 17p12
- Locus Type:
- gene with protein product
- Date approved:
- 1997-11-11
- Date modifiied:
- 2015-02-03
Related products to: MKK4 (Constitutively Active) Recombinant Adenovirus
Related articles to: MKK4 (Constitutively Active) Recombinant Adenovirus
- Pancreatic ductal adenocarcinoma (PDAC) is highly lethal and remains largely refractory to targeted therapy despite its near-universal dependence on oncogenic KRAS. Single-agent KRAS inhibitors often fail due to adaptive resistance mechanisms that emerge under pharmacologic pressure. Previous studies combining MAP2K4 inhibition with KRASG12C-targeted therapy determined that partial JNK suppression can enhance anticancer responses. Here, we extend this concept to PDAC, which is predominantly driven by KRASG12D mutations, and demonstrate that full JNK pathway inactivation restores sensitivity to KRAS inhibition in resistant cells. Using selective MAP2K4, MAP2K7, or combined inhibitors, we show that more extensive JNK suppression disables the feedback loop that reactivates KRAS signaling. In contrast, KRASG12D inhibitor-sensitive cells derive no benefit from JNK pathway inhibition, revealing a resistance-specific vulnerability amenable to therapeutic exploitation. - Source: PubMed
Publication date: 2026/09/07
Connors Gina MPham Thao DBecker Jeffrey HArgus Aria ABaba KenkichiKinoshita TakayoshiMunshi Hidayatullah GScheidt Karl A - Pleomorphic adenoma (PA) is the most common salivary gland benign tumor, with its molecular drivers elusive due to a lack of experimental models. This study aimed to decipher novel targets in PA by systematically integrating plasma protein quantitative trait loci (pQTL)-based Mendelian randomization (MR) with multi-omics profiling of parotid gland tissues. - Source: PubMed
Publication date: 2026/07/01
Fan YuchenMao SuningWang GuanruZhao GuileZhuang ShiyongYang FanLiu LiuLi HonglinLi ChunjieCao Yubin - Cellular senescence plays a critical role in physiological and pathological processes. This study aims to elucidate the contribution of cellular senescence-related genes to disease etiology. We investigated a cohort study of 439,501 individuals, which included 22 cancers and 9 non-cancer diseases. We found that HLA-E and HLA-G-associated senescence in epithelial and immune cells were specific oncogenic factors for prostate and lung cancers. MAP2K4 was implicated as a risk factor for breast cancer, while ZFP36L1 and STAT3 were associated with a reduced risk of inflammatory bowel disease (IBD). Notably, ETS2-mediated inhibition of the senescence-associated secretory phenotype (SASP) was associated with decreased disease risk. Furthermore, single-cell level analysis confirmed that the dynamics of these marked gene expressions in immune cells was related to reduced disease risk, while upregulation in epithelial cells correlated with increased disease risk. In parallel, co-localization analyses corroborated these associations, explaining potential regulatory mechanisms underlying disease risk variants. These findings enhance our understanding of how cellular senescence works on disease susceptibility and provide potential targets for therapeutic interventions and precision medicine approaches. - Source: PubMed
Publication date: 2026/08/30
Liu BinWu WeidongLiu ChangFeng PengyaLiu SimengGong ShanshanLi YingyingLi YaMi JunZheng PengyuanWen HongtaoXue XiaMi Yang - : Cabozantinib is a tyrosine kinase inhibitor that primarily targets MET. It has become an important drug in the treatment of renal cell carcinoma (RCC); however, many patients do not respond to cabozantinib treatment and there is no effective next-line therapy. In this study, we identified molecular-targeted drugs that exhibit synergistic effects with cabozantinib using CRISPR/Cas9 screening. : A kinome-wide synthetic lethal CRISPR/Cas9 screen was used to identify target molecules using 786-o RCC cells. A library was generated, and treatment with vehicle or cabozantinib was carried out, followed by next-generation sequencing to identify candidate genes. A combination index based on the Chou-Talalay method was used to evaluate the synergistic effect of cabozantinib through cell viability assays. Xenograft assays were conducted to determine the effect in vivo. : CRISPR/Cas9-based screening revealed four genes (, , , and ) that were candidates for synthetic lethality by cabozantinib in RCC cells. We focused on MEK1 because the MEK1 inhibitor cobimetinib has been approved for melanoma treatment. In a cell proliferation assay using 786-o and A498 RCC cells, the combination of cobimetinib and cabozantinib exhibited a synergistic effect. A xenograft assay also revealed a significant synergistic effect of cobimetinib and cabozantinib. : CRISPR/Cas9 screening identified MEK1 as a candidate for a synthetic lethal target with cabozantinib in RCC. The combined inhibition of MET/VEGFR and MEK1 suppressed compensatory MAPK reactivation and downregulated the PI3K-Akt pathway, including the survival-associated genes PPP2R3B and ATF6B, and produced significant tumor growth suppression in vivo. These findings highlight the potential of cabozantinib plus cobimetinib, an already-FDA-approved MEK inhibitor, as a readily translatable combination strategy to overcome cabozantinib resistance in RCC. - Source: PubMed
Publication date: 2026/07/12
Yoshino HirofumiFukuda IkumiEnokida HidekiSeki NaohikoGoto Yusuke - The rapidly accelerated fibrosarcoma/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (RAF/MEK/ERK) signaling cascade regulates cell proliferation and differentiation and is frequently dysregulated in cancer. Approximately 90% of RAF-mutant cancers harbor mutations in B-type rapidly accelerated fibrosarcoma (BRAF). Its proto-oncogenicity is attributed to a four-residue N-terminal acidic (NtA) motif. Although a long-standing model proposes that the NtA promotes activating asymmetric RAF dimerization, the model lacks structural support. Here, we present structures of NtA-mediated asymmetric BRAF dimers bound to their substrate MEK1. Cellular and biochemical data show that the NtA is not required for KRAS-mediated BRAF recruitment to the plasma membrane but is required for the fully catalytically active state. The structure capturing BRAF in a post-catalytic state bound to Ser222-phosphorylated MEK1 further supports this model. The combination of structural and cellular data corroborates the model of NtA-driven asymmetry in BRAF activation and resolves a long-standing disconnect between RAF cancer genetics and structural biology. - Source: PubMed
Publication date: 2026/07/21
Kondo YasushiNotbohm JudithNavas Camacho IgnacioNagy-Davidescu GabrielaMason ThomasMühle JonasStandfuss JörgPerica Tina