Ask about this productRelated genes to: MAP4K4 Blocking Peptide
- Gene:
- MAP4K4 NIH gene
- Name:
- mitogen-activated protein kinase kinase kinase kinase 4
- Previous symbol:
- -
- Synonyms:
- HGK, NIK, FLH21957
- Chromosome:
- 2q11.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-09-07
- Date modifiied:
- 2016-10-05
Related products to: MAP4K4 Blocking Peptide
Related articles to: MAP4K4 Blocking Peptide
- Transient Receptor Potential Melastatin 7 (TRPM7) is a 'chanzyme' with dual functions, acting both as a channel for divalent ions and as a serine/threonine kinase. Overexpression of TRPM7 has been linked to the development of various diseases, particularly cancers, making it a promising molecular target. Despite its relevance in oncogenesis, the phospho-regulatory network of TRPM7 remains largely unexplored, with limited evidence on its upstream kinases, downstream substrates, and site-specific phospho-regulated functions. - Source: PubMed
Publication date: 2026/06/01
Palollathil AkhinaMahin AlthafGopalakrishnan Athira PerunellySambreena AlimathShivamurthy Prathik BasthikoppaRaju Rajesh - Wilms' tumor (WT) is one of the most common pediatric abdominal malignancies. The RNA-binding protein heterogeneous nuclear ribonucleoprotein D (hnRNPD) is related to cancer progression through regulating target mRNA stability. Nonetheless, its expression profile and value for WT are largely unexplored. Human renal proximal tubular epithelial cells (RPTEC) and WT cells (17.94, HFWT) were employed as experimental models for exploring hnRNPD's effect on WT progression. Subsequently, potential downstream targets of hnRNPD were identified through bioinformatics analysis. Functional validation was performed in vitro by modulating hnRNPD and its candidate targets via gene silencing and overexpression methods. Alterations in gene expression was analyzed through qRT-PCR as well as Western blot. Besides, CCK-8 was conducted to evaluate cell proliferation, whereas scratch and Transwell assays to determine cell migration alongside invasion separately. Additionally, critical epithelial-mesenchymal transition (EMT)-associated protein expression, namely E-cadherin, N-cadherin, alongside vimentin, was detected to assess regulatory impact of hnRNPD on the EMT process. hnRNPD mRNA and protein expression significantly elevated within 17.94 and HFWT cells than in RPTEC cells. Silencing of hnRNPD in 17.94 cells inhibited cell proliferation, migration, and invasion. Concurrently, N-cadherin and Vimentin protein levels declined, and E-cadherin protein level increased. Conversely, overexpression of hnRNPD in HFWT cells markedly enhanced their malignant phenotypes and promoted EMT. Bioinformatics analysis identified mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) as a potential downstream target of hnRNPD in WT. Mechanistically, hnRNPD overexpression extended the half-life of MAP4K4 mRNA, and a specific physical interaction between hnRNPD protein and MAP4K4 mRNA was observed. Functional rescue experiments further demonstrated that silencing MAP4K4 inhibited tumor malignant progression, while overexpression of MAP4K4 reversed the tumor-suppressive effects induced by hnRNPD silencing. hnRNPD may promote EMT in WT cells by stabilizing MAP4K4 mRNA, suggesting a critical role for the hnRNPD-MAP4K4 axis in driving tumor progression. - Source: PubMed
Publication date: 2026/06/03
Li GangLiao ManBao HaibinXu HaolunWang JunZhang ManLi CanZheng TianYang Chunlei - Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting side effect of cancer treatment, yet the lack of predictive human models continues to hinder therapeutic progress. Here, we establish a scalable and reproducible model of paclitaxel-induced axon degeneration and neurotoxicity in human iPSC-derived sensory neurons, suitable for high-throughput identification of neuroprotective compounds. Using this platform, we screen a library of 192 kinase inhibitors and identify 19 hits that commonly inhibit three STE20 kinases-MAP4K4, MINK1, and TNIK. Genetic knockdown studies reveal that multi-kinase inhibition of these kinases is required for neuroprotection against paclitaxel. Consistently, selective pharmacological inhibition of the identified STE20 kinases rescues paclitaxel-induced axon degeneration in iPSC-derived sensory neurons and primary human dorsal root ganglia (DRG) and preserves intraepidermal nerve fiber density in a mouse model of CIPN. Together, these findings establish a translational human sensory neuron platform that enables target validation and drug discovery for CIPN. - Source: PubMed
Publication date: 2026/05/06
Petrova VeselinaMills Caitlin EHug ClemensCetinkaya-Fisgin AyselSplaine JenniferFouladzadeh SepidehHakim SaraPowell RasheenZhen ShannonChung MirraBradshaw Gary ADeng TaoSingec IlyasWang QingKawaguchi RikiJonnagaddala HarathiBarrett Lee BSmith Jennifer AKalocsay MarianGyori Benjamin MHoke AhmetSorger Peter KWoolf Clifford J - Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive condition and a leading driver of global liver-related morbidity. Its advanced form, metabolic dysfunction-associated steatohepatitis (MASH), is characterized by hepatic steatosis, inflammation, hepatocellular ballooning, and fibrosis. This study aimed to define the significance of MAP4K4 (mitogen-activated protein kinase kinase kinase kinase 4) as a therapeutic target and to evaluate a novel small-molecule inhibitor, glucosyl pyrrolo-pyrimidinone (GPPD), for the mitigation of MASH. - Source: PubMed
Publication date: 2026/05/04
Ampadu FelixPatil NikhilEeda VenkateswararaoRus IuliaJung WoncheolAbu Shukair Hassan MAli AnzaAguilar-Sanchez YurianaOh Tae GyuAwasthi VibhuduttaJoshi Aditya D - The incidence of obesity and male infertility continues to rise, and a complex pathophysiological association exists between the two. However, the comorbid molecular mechanisms remain incompletely elucidated. In this study, bioinformatics and machine learning methods were integrated to systematically explore the shared mechanisms of obesity and male infertility, and to predict natural compounds and TCMs with therapeutic potential based on multi-omics data. Datasets of male infertility and obesity were obtained from the GEO database, and 43 intersecting genes were identified through differential expression analysis. Using three machine learning algorithms, including random forest, least absolute shrinkage and selection operator(LASSO) regression, and support vector machine(SVM), five Hub genes(MAP4K4, GPT2, ADSSL1, PAIP2, and GINS3) were screened. The combined diagnostic model achieved an area under the curve(AUC) greater than 0.8, indicating good diagnostic performance. Functional enrichment analysis revealed that these genes are mainly involved in key biological processes such as amino acid metabolism, cell migration, and DNA replication. Immune infiltration analysis showed a significant upregulation of central memory CD4~+ T cells in both diseases, suggesting that chronic immune activation is an important basis for their comorbidity. Single-cell sequencing and pseudotime analyses demonstrated disordered cell differentiation trajectories in the adipose tissue of obese patients and the testicular tissue of infertile patients. Based on the connectivity map(CMap) database, ten natural compounds, including berberine, curcumin, and ginsenosides, were predicted and further validated by molecular docking to have strong binding affinities with the Hub genes. Integration with the traditional Chinese medicine systems pharmacology(TCMSP) platform enabled the construction of a "target-natural compound-herbal medicine" interaction network, identifying 38 corresponding herbal medicines. Property and meridian analysis indicated a predominance of warm nature, sweet flavor, and liver meridian tropism, consistent with the TCM therapeutic principles of "resolving phlegm and dampness, strengthening the spleen, and tonifying the kidney". This study reveals, at the molecular level, the comorbid mechanisms of obesity and male infertility in immune-inflammatory regulation and cell differentiation dysfunction, providing a theoretical basis and potential drug targets for precise TCM intervention in obesity-related male infertility. - Source: PubMed
Gong Zhuo-ZhiFeng Qiu-JianGao Qing-HeWang FuGuo JunLiu Sheng-Jing