Ask about this productRelated genes to: DNAJB6 Blocking Peptide
- Gene:
- DNAJB6 NIH gene
- Name:
- DnaJ heat shock protein family (Hsp40) member B6
- Previous symbol:
- LGMD1D
- Synonyms:
- MRJ
- Chromosome:
- 7q36.3
- Locus Type:
- gene with protein product
- Date approved:
- 2001-03-09
- Date modifiied:
- 2015-11-19
Related products to: DNAJB6 Blocking Peptide
Related articles to: DNAJB6 Blocking Peptide
- The amyloid-β (Aβ) peptide is an intrinsically disordered protein whose self-association into toxic oligomers underlies Alzheimer's disease. Because of its dynamic and heterogeneous nature, identifying the conformational states that nucleate aggregation remains a central challenge. In this work, we introduce a chemically interpretable descriptor of amyloidogenic propensity derived from self-docking analyses of conformational ensembles generated through temperature-replica exchange molecular dynamics (T-REMD) using different and complementary force fields. This descriptor classifies individual conformers within the generated ensembles according to their intrinsic aggregation tendency, enabling the identification of metastable, aggregation-prone states. The resulting ensembles reproduce experimental observables, and their classification based on amyloidogenic propensity provides a consistent structural basis for the rationalization and study of these metastable conformers. As a test, we demonstrate that the molecular chaperone DNAJB6, experimentally known to bind amyloidogenic conformations, preferentially interacts with aggregation-prone conformers, thus supporting both the proposed protocol and the consistency of the classification scheme. More broadly, this framework outlines a potentially generalizable strategy to identify metastable states in intrinsically disordered proteins as prospective pharmacological targets to help develop drugs or biomolecules capable of inhibiting the early stages of their aggregation. - Source: PubMed
Publication date: 2026/04/14
Bini MargheritaTozzini ValentinaBellucci Luca - Identifying clinical outcome assessments (COAs) that are able to detect change in functional abilities over time in the limb girdle muscular dystrophy (LGMD) population is critical for managing disease progression in addition to determining drug efficacy in the context of anticipated therapeutic trials. Through the Genetic Resolution and Assessments Solving Phenotypes in LGMD (GRASP-LGMD) Consortium, 42 participants with LGMDR1 were enrolled in a 12-month natural history study across 11 international sites. Each participant completed a battery of COAs, including the North Star Assessment for Limb Girdle-Type Muscular Dystrophies (NSAD), 100-meter timed test (100 m), Performance of the Upper Limb (PUL), and 4-Stair Climb (4SC) in addition to several patient-reported outcome measures (PROM) across three time points in this year-long study. Participants with LGMDR1 demonstrate significant decline in the 100 m, NSAD, PUL, and 4SC over a 12-month time period. The rate of decline was greater in those considered to be higher functioning (10-meter time <12 s) while genetic variant types did not appear to significantly influence the rate of decline in our cohort. A combination of COAs is determined to be the best approach at measuring functional change over time in patients with LGMDR1. - Source: PubMed
Publication date: 2026/04/01
Hunn Stephanie MFindlay Andrew RAlfano Lindsay NJones AileenButler AmandaLowes Linda PIammarino Megan AReash Natalie FPietruszewski LindsaySasidharan SandhyaCurrence MelissaStatland Jeffrey MStrahler TaliaWill RobertWicklund MatthewDixon StacyAugsburger ReneeMozaffar TahseenLaubscher Katie MMockler Shelley R HMathews Katherine DStinson NikiaLeung Doris GStark Molly MHorton Rebecca AKang Peter BJames Meredith KClause AmandaWeihl Conrad CJohnson Nicholas E - Transmissible gastroenteritis virus (TGEV) is a porcine enteropathogenic coronavirus that causes severe intestinal inflammation and diarrhea in pigs, leading to substantial economic losses to the swine industry worldwide. Inflammation is a major cause of death in pigs infected with TGEV. However, the role of host-mediated inflammatory responses in TGEV pathogenesis remains poorly understood. Here, we report for the first time that the heat shock protein HSP40 (DNAJB6) is highly expressed in the jejunum and ileum of Wuzhishan pigs during TGEV infection, and that its transcription is activated by the transcription factor YY1. Gain- and loss-of-function experiments revealed that HSP40 enhances both the inflammatory response and TGEV replication by modulating NF-κB signaling. Mechanistically, HSP40 facilitates the recruitment of β-TRCP, an E3 ubiquitin ligase of IκB, promoting its interaction with IκB and subsequent proteasomal degradation. Under basal conditions, IκB binds to and sequesters p65 (RelA) in the cytoplasm, preventing its nuclear translocation and transcriptional activity. During TGEV infection, HSP40-mediated degradation of IκB releases p65, enabling its nuclear translocation and the transcriptional activation of multiple inflammatory genes. Furthermore, β-TRCP was found to be essential for HSP40-mediated production of inflammatory cytokines. Collectively, these findings uncover a pivotal role for HSP40 in regulating inflammation and viral replication during TGEV infection, and suggest that targeting HSP40 may represent a promising therapeutic approach against TGEV. - Source: PubMed
Publication date: 2026/03/06
Gao ShuaiChao ZheCao ZongxiWang FengSun RuipingLiu Guangliang - The chaperone DNAJB6 inhibits aggregation of several amyloid proteins, such as α-synuclein and huntingtin, which are involved in neurodegenerative diseases. Here, we designed a cell-based assay to measure DNAJB6 dimerization in HEK293 cells by fluorescent resonance energy transfer (FRET), as previous studies suggest that the activity of DNAJB6 is dependent on dimerization. The HEK293 cells were engineered to stably express DNAJB6 coupled to cyan fluorescent protein and yellow fluorescent protein, respectively. A platereader format was used to analyze the FRET signal from dimerization. Stimulation with Tunicamycin, a positive control that induces protein misfolding, or with α-synuclein preformed fibrils, increased the FRET signal significantly, in these cells. This increase in FRET signal reflects enhanced dimerization activity, which is suggested to correlate with chaperone activity. To our knowledge, this study is the first to measure a DNAJ protein dimerization activity using a FRET-based approach. These cells could serve as an experimental platform to screen for compounds that modulate DNAJB6 dimerization activity, which in the future may aid in identifying potential therapeutic targets. - Source: PubMed
Publication date: 2026/02/04
Gelman AnnaQuintino LuisNordberg ManjaNyeng PiaBrudek TomaszNielsen Leif KofoedHansen Christian - Nucleated erythroid cells (NECs) have emerged as active participants in immune responses in addition to their canonical oxygen transport function. The subpopulations and immune heterogeneity of chick erythroid cells (ch-ECs) upon infection have not been fully characterized. Single-cell RNA sequencing (scRNA-seq) was used to profile ch-ECs in chicks infected with avian pathogenic (APEC). Unsupervised clustering uncovered ten distinct ch-EC subpopulations (C1-C10), with significant compositional shifts between infected and control groups. Pseudotime analysis revealed a developmental continuum: C1, C3, C5, and C9 as early progenitors; C2, C4, C6, C7, and C10 as mature erythroid cells; and C8 as a naive population. We revealed 62 immune-related genes, including protein kinases and heat shock proteins, and subpopulation-specific differentially expressed genes (DEGs) linked to immune functions. SCENIC analysis revealed Fos, Srf, and Stat3 as key transcription factors with elevated regulon activity and specificity following infection. Subpopulations C2, C4, C6, and C7, which exhibited marked abundance changes, were scrutinized for immune relevance through integrated multi-omics analysis. Immune-related genes including , , , , , , , and were identified. Enrichment analysis indicated activation of the MHC class I antigen presentation pathway, while pathways such as Mitogen-Activated Protein Kinase (MAPK) signaling, NOD-like receptor (NLR) signaling, and the heat shock response were found to be suppressed. In conclusion, this study delineates the immune gene repertoire and signaling networks of ch-ECs during APEC infection, offering new perspectives on NEC immunoregulatory functions. - Source: PubMed
Publication date: 2026/01/07
Cai FujuanWang XianjueWang ChunzhiWang YuzhenZhang Wenguang