Ask about this productRelated genes to: NUDC antibody
- Gene:
- NUDC NIH gene
- Name:
- nuclear distribution C, dynein complex regulator
- Previous symbol:
- -
- Synonyms:
- NudC
- Chromosome:
- 1p36.11
- Locus Type:
- gene with protein product
- Date approved:
- 1999-01-22
- Date modifiied:
- 2016-06-13
Related products to: NUDC antibody
Related articles to: NUDC antibody
- V(D)J recombination is the fundamental process by which developing T and B lymphocytes generate diverse antigen receptors, enabling adaptive immunity. This tightly regulated program operates exclusively in lymphoid precursors during G1 phase and depends on the lymphocyte specific RAG1-RAG2 recombinase to introduce programmed DNA double-strand breaks at recombination signal sequences, followed by repair through the classical non-homologous end-joining (c-NHEJ) pathway. Disruption of any step in this molecular choreography compromises antigen receptor diversity and underlies a spectrum of inborn errors of immunity (IEI), ranging from severe combined immunodeficiency (SCID) to immune dysregulation with autoimmunity and granulomatous disease. In this review, we place disorders of V(D)J recombination within the broader framework of T-cell development, detailing the temporal waves of recombinase activity, chromatin accessibility, and DNA damage responses that guide thymocyte differentiation. We discuss pathogenic variants affecting the cleavage phase (RAG1, RAG2, and the recently identified RAG co-chaperone NudC domain-containing 3, NUDCD3), end processing (ARTEMIS), ligation and repair (LIG4, XLF, XRCC4, PRKDC), and genome surveillance pathways (ATM, MRN complex, RNF168), highlighting genotype-phenotype correlations and mechanisms driving immune deficiency and dysregulation. We briefly review recent diagnostic advances, including newborn screening using T-cell receptor excision circles, repertoire sequencing, and functional assays, alongside current therapeutic strategies. Finally, we outline key unanswered questions and argue that continued integration of clinical observation with molecular discovery is essential to improve outcomes and deepen understanding of adaptive immune development. - Source: PubMed
Publication date: 2026/03/28
Schim van der Loeff InaAhuja ManishaChen RuiPatane EleonoraHambleton Sophie - Heat shock proteins (HSPs) are evolutionarily conserved, yet their functions in plant growth and development remain incompletely characterized. Here, we demonstrate that a HSP90 co-chaperone PpNudC6 is essential for directional cell expansion in the moss Physcomitrium patens. We generated ppnudc6 mutants and characterized their phenotypes. Dysregulation of PpNudC6 disrupts cellulose microfibril organization and cell wall stiffness gradients, as shown by scanning electron microscopy and atomic force microscopy, ultimately resulting in shortened and thickened protonemal cells. Mechanistically, this phenotype is mediated by disrupted reactive oxygen species (ROS) homeostasis. Loss of PpNudC6 function induces ectopic activity of the NADPH oxidase PpRbohD in protonemata, leading to abnormal ROS accumulation. Pharmacological inhibition of NADPH oxidases by diphenyleneiodonium rescues mutant phenotypes, confirming ROS overproduction as the primary driver of developmental defects. Furthermore, PpNudC6 interacts with the scaffold protein PpRACK1B and the co-chaperone PpSGT1, suggesting a multisubunit complex that modulates respiratory burst oxidase homolog (Rboh) activity. In summary, our findings reveal a chaperone-mediated regulatory module that mediates the production of ROS, thereby maintaining cell wall mechanical anisotropy required for directional expansion. This work provides insights into a novel role of HSP complexes in regulating directional cell expansion and links redox homeostasis to cell wall mechanics during moss development. - Source: PubMed
Publication date: 2026/02/05
Ren ShulinWang HaiyanJiao YulingWang Ying - The development and progression of cardiometabolic diseases and depression multimorbidity involves pathophysiological processes across multiple organs. Using multi-organ imaging data from 31,246 UK Biobank participants, we investigate the multi-organ manifestations and their phenotypic connections and shared genetic architecture underlying the multimorbidity. Phenotypic analyses identify seven abdominal, 16 cardiac, and 107 brain traits forming 1418 abdomen-heart-brain cliques, with liver volume, myocardial wall thickness, and white matter hyperintensity volume as central nodes. Genetic analyses reveal 43 distinct genomic loci (21 novel) shared by these cliques, with the most widely shared loci mapped to genes NUDC, ARID1A, and CRHR1. The 224 protein-coding genes mapped by these loci are enriched in 39 biological processes related to cardiometabolic and neuropsychiatric functions, with 15 genes expressed across liver-heart-brain axis tissues. Combining biochemical and multi-organ imaging indicators significantly improves multimorbidity prediction. These findings uncover multi-organ network underlying physical-mental multimorbidity and highlight the necessity of holistic management. - Source: PubMed
Publication date: 2026/01/07
Wang JingxuanLiu MianxinLiu FengYang GuangruiYuan ZhongshangHuang HaoZhang ZixuanWang LilongWu YeFan WenliangShi ShuxiaoChen MengJiang XuanweiYan QiaolingLan JunLiu XiaomingRong ShuangFeng NannanZhong Victor W - Isoniazid (INH) and ethionamide (ETH) are important antitubercular analogs that inhibit mycolic acid synthesis. However, () exhibits intrinsic resistance to both drugs. The molecular mechanisms underlying this resistance remain poorly understood. We identified c (), encoding a functional NADH pyrophosphatase NudC that hydrolyzes drug-NAD adducts, as being crucial for intrinsic resistance to INH and ETH in . Susceptibility to both antibiotics was markedly enhanced upon either deleting or introducing the P226Q point mutation in this conserved residue. High-performance liquid chromatography-mass spectrometry analysis further demonstrated that the deletion of resulted in accumulation of the ETH-NAD adduct and a decrease in its hydrolysis rate in ETH-treated . Size-exclusion chromatography analysis revealed that wild-type NudC predominantly forms dimers, whereas the P226Q mutant exists mainly as monomers, consistent with a loss of enzymatic function. A pivotal proline at position 226 governs its dimerization and enzymatic activity. To complement the knockout strain, we introduced seven different versions of the gene separately, each producing a protein with a point mutation at different key residues: D133A, N148D, F156A, F193A, E207Q, E211Q, and R231Q. None of them restore the resistance to INH and ETH, illustrating that these sites are also critical for the catalytic activity of NudC. This discovery elucidates a previously unrecognized mechanism of drug resistance in and highlights NudC as a potential target for therapeutic intervention.IMPORTANCE poses a serious therapeutic challenge due to its extensive drug resistance. This study elucidates the molecular mechanism behind its intrinsic resistance to the critical antitubercular drugs isoniazid and ethionamide. We identify the NudC (MAB_3513c) enzyme as a central resistance factor that functions by hydrolyzing the active drug-NAD adducts. Crucially, we demonstrate that NudC's enzymatic activity, dependent on its dimerization and key catalytic residues, is essential for this resistance mechanism. This finding establishes NudC as a promising therapeutic target for combating this highly drug-resistant pathogen. - Source: PubMed
Publication date: 2025/11/28
Wang ShuaiZhang XiaofanFang XiangeHameed H M AdnanMalik AbdulLong LihuaGao YaminFang CuitingTian XirongHu JinxingWang XingyueFeng LiqiangZhang Tianyu - Breast cancer heterogeneity stems from diverse molecular alterations, including proteostasis loss due to chaperone system dysfunction. However, the impact of impaired chaperone activity on proteomic changes and tumorigenesis remains unclear. Here, characterized the expression patterns of major chaperone families and mapped their client protein interactions to elucidate their role in shaping tumor biology. We identified 53 chaperones expressed in breast tissue, of which 26 were differentially expressed between tumor and non-tumor samples. Using validated protein interaction data and machine-learning predictions, coupled with molecular docking, we constructed protein-protein interaction (PPI) networks for each chaperone family and subsequently performed enrichment analyses to assess their involvement in cancer-related pathways. Each chaperone family's PPI network comprised a distinct set of client proteins and was enriched in different biological pathways and processes. The HSP70 system PPI network included LYN, NFKB1, and PARP1, and was related to DNA repair and immunomodulation through interleukin and cytokine signaling. Although a partial overlap of client proteins was observed between the HSP70 and HSP90 sets, HSP90 was also associated with particular client proteins, including TRAF2, PDGFRB, and NUDC, which were enriched in MAPK and PI3K/AKT/mTOR signaling pathways, as well as epithelial-to-mesenchymal transition and cell cycle control. Our results also indicate an association between CCT/TRiC chaperonins and the regulation of tubulin/actin, supporting their involvement in cytoskeleton dynamics, the mitotic spindle, chromosome segregation, and autophagy/aggrephagy. Overall, our findings expand the repertoire of chaperone client proteins and provide insights into how chaperone dysregulation influence breast cancer biology, highlighting their potential as therapeutic targets. - Source: PubMed
Publication date: 2025/11/24
Azevedo Alexandre Luiz Korte dePereira Mateus Vinicius OliveiraRibeiro Enilze Maria de Souza FonsecaGomig Talita Helen Bombardelli