Ask about this productRelated genes to: NEK4 antibody
- Gene:
- NEK4 NIH gene
- Name:
- NIMA related kinase 4
- Previous symbol:
- STK2
- Synonyms:
- NRK2, pp12301
- Chromosome:
- 3p21.1
- Locus Type:
- gene with protein product
- Date approved:
- 1995-05-10
- Date modifiied:
- 2016-01-13
Related products to: NEK4 antibody
Related articles to: NEK4 antibody
- NIMA-related kinase 4 (NEK4) is a serine/threonine kinase implicated in microtubule stabilization, cilia function, and DNA damage response (DDR), with emerging roles in cancer progression through context-dependent effects on proliferation, epithelial-to-mesenchymal transition (EMT), and metastasis. Despite its significance, site-specific phosphorylation dynamics of NEK4 remain underexplored. Here, we conducted a comprehensive computational phosphoproteomic analysis by curating Class-1 phosphosites from over 3800 public datasets, identifying NEK4 phosphosites, including four predominant sites (S563, S661, S461, S639) outside the kinase domain that exhibit high detection frequencies and differential regulation. Coregulation analysis revealed phosphosites in other proteins (PsOPs) that coordinate with these NEK4 sites, linking them to DDR pathways (e.g., via interactions with DNA-PK complex components), EMT signaling, microtubule organization, and mitochondrial function. Network mapping integrated predicted upstream kinases (e.g., CDK13, RPS6KA1/3), downstream substrates (e.g., MKI67, INCENP), and binary interactors (e.g., TMPO, RRP1B), highlighting NEK4's integration into cancer-associated networks involving cell cycle regulation, apoptosis, and autophagy. Functional enrichment underscored NEK4's potential in modulating genotoxic stress responses and tumorigenic reprogramming. These findings provide a phospho-centric framework for NEK4 signaling, positioning it as a therapeutic target in DDR-defective and EMT-driven cancers, and lay the groundwork for experimental validation of its site-specific roles. - Source: PubMed
Publication date: 2026/06/24
Kashipatna Spoorthi SathishPai ApoorvaDcunha LeonaSamseera UmmarGopalakrishnan Athira PerunellyRajeev Athira CRaju Rajesh - Maternal embryonic leucine zipper kinase (MELK) is a serine/threonine kinase frequently overexpressed in aggressive cancers, yet the precise mechanisms governing its activation and signaling specificity remain poorly understood. Here, we present the first phosphosite-resolved co-regulation atlas of MELK through integrative meta-analysis of 3,825 global human phosphoproteomics datasets. Three phosphosites-S356, S505, and S529-emerge as dominant regulatory nodes, exhibiting high detection frequency and distinct co-regulation patterns. S356 and S505 form a tightly coupled proliferative-mitotic axis controlled by convergent Mitogen-Activated Protein Kinase Kinase (MAPK), Ribosomal S6 Kinase (RSK), Calcium/Calmodulin-dependent protein Kinase (CaMK), Hippo-related, and spindle-checkpoint kinases (NIMA-related kinase 4 (NEK4), Threonine Tyrosine Kinase/Monopolar Spindle 1 Kinase (TTK/MPS1)), whereas S529 functions as a partially antagonistic stress- and polarity-responsive module. Marker of Proliferation Ki-67 (MKI67) phosphosites co-vary with all three MELK sites across virtually all proliferative contexts, establishing a direct mechanistic link between MELK activity and clinical proliferation markers. Extensive networks of co-regulated upstream kinases, phosphatases, binary interactors, and downstream substrates further reveal functional segregation: S356/S505 primarily drive cell-cycle progression and chromatin organization, while S529 integrates calcium, metabolic, and cytoskeletal polarity signals. Kaplan-Meier survival analysis across TCGA cohorts further revealed that high expression of MELK, MKI67, and the mitotic checkpoint kinase TTK consistently predicts poor overall and disease-free survival in lung adenocarcinoma and hepatocellular carcinoma, reinforcing the strong phosphodynamic coupling between MELK activity and clinical proliferation markers. By demonstrating that MELK signaling is orchestrated through modular, site-specific phosphorylation logic rather than total protein abundance, this work establishes a new paradigm for understanding and therapeutically targeting this enigmatic oncogenic kinase. - Source: PubMed
Publication date: 2026/05/08
Khan Noreen AFahma AmalMahin AlthafGopalakrishnan Athira PerunellyShivamurthy Prathik BasthikoppaUmmar SamseeraRajeev Athira CRaju Rajesh - Anxiety disorders and posttraumatic stress disorder (PTSD) often occur alongside signs of accelerated biological aging, yet the molecular pathways that connect genetic liability to synaptic and circuit-level dysfunction remain unclear. We performed a multi-gene-set transcriptome-wide association study using large-scale genome-wide association study (GWAS) summary statistics for anxiety disorders and PTSD, with a focus on curated aging-related pathways across brain regions involved in fear, reward, memory, and stress regulation. The analysis identified 185 significant enrichments, with strong cross-disorder concordance in senescence, telomere maintenance, and mitochondrial modules. PTSD showed a distinctive negative signature in nicotinamide adenine dinucleotide (NAD) metabolism and sirtuin-related pathways, most prominently driven by sirtuin 3 (SIRT3), together with evidence of sterile alpha and Toll/interleukin-1 receptor motif-containing 1 (SARM1)-linked axonal and synaptic vulnerability. Anxiety disorders showed stronger enrichment in mitochondrial intrinsic apoptosis and inflammatory-redox signaling, alongside glutamatergic and astrocytic plasticity changes. Both conditions shared senescence and deoxyribonucleic acid (DNA)-damage programs, with NIMA-related kinase 4 (NEK4) emerging as a common driver. These pathways converged on complement-mediated pruning and presynaptic remodeling, suggesting a mechanistic bridge from cellular aging to fear and reward circuit dysfunction. Together, the findings support an association-based model in which genetic liability for anxiety disorders and PTSD converges on stress-aging biology at the synapse, while diverging by disorder. This framework points to candidate biologically distinct subtypes and offers practical opportunities for biomarker development, patient stratification, and subtype-guided therapeutic strategies. These subtype labels are proposed biological hypotheses rather than validated clinical categories. - Source: PubMed
Publication date: 2026/06/12
Cheung Ngo - Lung adenocarcinoma (LUAD) is characterized by high heterogeneity and insidious early-stage progression, leading to a dismal clinical prognosis and posing a formidable challenge in current oncological research. Although the Thioredoxin domain-containing (TXNDC) family is involved in various cancers, the role of TXNDC15 in LUAD remains unclear. Here, we show that TXNDC15 is downregulated in LUAD and predicts better survival. Functional assays reveal that TXNDC15 suppresses proliferation by inducing G2/M phase arrest. Mechanistically, TXNDC15 interacts with the mitotic kinase NEK4, thereby orchestrating the G2/M checkpoint circuitry to restrict malignant progression. These findings highlight the TXNDC15-NEK4 factor as a pivotal regulatory node in LUAD progression. - Source: PubMed
Publication date: 2026/05/20
Wang YingFeng XinYuan LeiXiao Wenming - Meiosis is a conserved yet evolutionarily varied process underpinning sexual reproduction in eukaryotes. In the malaria parasite Plasmodium, meiosis is unconventional: it occurs immediately after fertilisation (post-zygotic) and must be coordinated with the transformation of the zygote into a motile ookinete. The mechanisms synchronising these meiotic and morphogenetic programmes remain unknown. Here, we identify the Plasmodium berghei NIMA-related kinase NEK4 as a key regulator that couples meiotic initiation with zygote morphogenesis. Using ultrastructure expansion microscopy, we show that NEK4 accumulates at the microtubule-organising centre (MTOC) and the apical polar complex (APC) shortly after fertilisation, preceding the assembly of perinuclear and cortical microtubules. We reveal that Plasmodium zygotes undergo MTOC-associated nuclear migration, analogous to the meiotic nuclear movement in fission yeast. Deletion of the Pbnek4 gene results in complete developmental arrest: MTOC duplication and microtubule formation are blocked, chromatin remains uncondensed, and nuclear migration and cell polarity fail to establish. Transcriptomic and phosphoproteomic analyses reveal that absence of NEK4 causes a collapse in transcriptional and phosphoregulatory networks governing meiosis and cytoskeletal organisation, leading to reduced expression and phosphorylation of important players, including HOP1, REC8, and AP2-O. These findings establish NEK4 as a key regulator driving meiotic entry and zygote maturation. - Source: PubMed
Publication date: 2026/05/12
Yanase RyujiHair MollyZeeshan MohammadFerguson David J PBrady DeclanPasquarello CarlaBottrill AndrewBhanvadia SuhaniNeal ArmundTromer Eelco CLe Roch Karine GHainard AlexandreHolder Anthony AVaughan SueGuttery David STewari Rita