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
- : 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 - Protein S-palmitoylation is a reversible lipid post-translational modification that dynamically controls protein localization, trafficking, receptor microdomain organization, autophagy and metabolic signalling. In osteoarticular tissues, this modification provides a plausible biochemical mechanism through which osteoclasts, osteoblast-lineage cells, osteocytes, chondrocytes, synoviocytes and skeletal-muscle cells integrate inflammatory, mechanical and metabolic cues. This review synthesizes current evidence linking S-palmitoylation and depalmitoylation to osteoarticular cell signalling and metabolic adaptation. We focus on experimentally supported mechanisms, including ZDHHC-mediated palmitoylation; depalmitoylation by APT, ABHD and PPT enzymes; palmitoylation-sensitive osteoclast differentiation; inflammatory priming of macrophage-derived osteoclast precursors; BMP/SMAD and organelle-contact-site signalling in osteoblast-lineage cells; ZDHHC11-dependent chondrocyte protection; ZDHHC4-mediated palmitoylation of CCDC50 followed by autophagic clearance of MAP2K4/MKK4; inflammasome regulation; CD36-associated lipid uptake; and palmitoylation-dependent transporter localization and turnover. We distinguish direct skeletal and joint evidence from mechanistic analogues derived from immune, neural, metabolic and cancer systems. We also clarify the distinction between reversible cysteine S-palmitoylation, broader S-acylation and other lipid modifications. Major barriers include incomplete definition of enzyme and substrate relationships, false-positive risk in palmitoyl-proteomic workflows, limited temporal resolution, insufficient validation in primary human tissues, uncertain tissue specificity and the off-target effects of non-selective palmitoylation inhibitors. A cell-biochemistry-centred view of the dynamic balance between palmitoylation and depalmitoylation may clarify how lipid modification regulates osteoarticular cell function and may help prioritize experimentally testable, substrate-specific mechanisms for future validation in osteoarthritis, osteoporosis and inflammatory joint disease. - Source: PubMed
Publication date: 2026/07/20
Huang XinqiWei XinpengTao YunHuang ZhimaoZhao ZhiheCen Xiao - Ketamine (KET) addiction has already been a serious problem all over the world, which could induce neurological and psychological harm. Levo-tetrahydropalmatine (l-THP), a major alkaloid extracted from the Chinese medicinal plants and , has been shown to attenuate ketamine (KET) induced conditioned place preference (CPP) in rats. Nevertheless, the precise mechanism remains unknown, and further research is necessary. - Source: PubMed
Publication date: 2026/06/29
Du YanGao Xing-CuiMa QingLi BeiChen YantingSu Hong-LiangDu LiLiang Tai-Gang - It is crucial that cancer patients receive the proper medication dosage. Too high of a dose can be toxic; too low of a dose will not effectively kill cancer cells. Accurate dosing requires a method to monitor drug levels and thereby guide dose adjustments. However, currently most cancer drugs do not have such a method available. To address this problem, I developed a new generalized method for drug measurement, a "modified thermal shift assay," based on observing the degree of thermal stabilization caused by drug present in the specimen binding to protein probe derived from that drug's intended target. We provided proof of concept that this method can measure the levels of the cancer drug trametinib, an inhibitor of MEK1 used to treat melanoma. However, due to the high affinity of MEK1 binding to trametinib, this initial formulation of this assay was highly sensitive but also saturated at low drug concentrations. To address this, I have modified this assay by expressing and purifying a series of mutant MEK1 proteins with reduced trametinib binding affinities. Utilization of these mutant MEK1 probes in parallel with wildtype MEK1 greatly increased the dynamic range and precision of the assay. Validation studies of this modified assay demonstrated that it displays a <12% coefficient of variation across over 5 logs, characteristics superior to current clinical drug monitoring assays. This assay only requires widely available equipment, is simple and rapid to conduct, and can be easily generalized to measure other drugs, demonstrating that this approach could provide the first generalizable method for clinical measurement of drug concentrations to guide dosing and improve the safety of a wide variety of drugs. - Source: PubMed
Publication date: 2026/07/10
Greenblatt Ethan B - Leiomyosarcoma is a rare and aggressive malignant smooth muscle tumor with limited treatment options and poor outcomes. Large-scale molecular characterization is needed to better understand tumor biology and support precision oncology, as prior studies have been limited by small cohort sizes, single-institution data, and restricted gene panels. This study aimed to characterize clinicogenomic features of leiomyosarcoma using the AACR Project GENIE 19.0 public dataset. - Source: PubMed
Ali HennaChander CinthiyaTorbenson ElijahHsia BeauSilberstein Peter T