A5003366722- Ubiquitin and proteasome pathways
- Neonatal Respiratory Health Research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Cancer-related gene regulation
- Autophagy in Disease and Therapy
- Cell death mechanisms and regulation
- Epigenetics and DNA Methylation
- Congenital Diaphragmatic Hernia Studies
- Pediatric health and respiratory diseases
- Peptidase Inhibition and Analysis
- Endoplasmic Reticulum Stress and Disease
- Histone Deacetylase Inhibitors Research
- Respiratory and Cough-Related Research
- Liver physiology and pathology
- Trypanosoma species research and implications
- COVID-19 Clinical Research Studies
- NF-κB Signaling Pathways
- Mitochondrial Function and Pathology
- IL-33, ST2, and ILC Pathways
- Bacterial biofilms and quorum sensing
- SARS-CoV-2 and COVID-19 Research
- Immune Response and Inflammation
- Asthma and respiratory diseases
- Immune cells in cancer
- Cardiac Ischemia and Reperfusion
National Yang Ming Chiao Tung University
2025
University of Pittsburgh
2015-2024
VA Pittsburgh Healthcare System
2020-2024
UPMC Montefiore
2015-2021
Shanghai Jiao Tong University
2015
Institute of Hydrobiology
2015
Chinese Academy of Sciences
2015
Zhejiang Ocean University
2015
Jinan University
2015
Juntendo University
1998-2001
The inflammasome is a multiprotein complex that augments the proinflammatory response by increasing generation and cellular release of key cytokines. Specifically, NALP3 requires two-step signaling, priming activation, to be functional cytokines IL-1β IL-18. process, through unknown mechanisms, increases protein levels pro-IL-1β in cells. Here we show LPS lifespan without significantly altering steady-state mRNA human exposure reduces ubiquitin-mediated proteasomal processing inducing an E3...
The pandemic of coronavirus disease 2019 (COVID-19) has been the foremost modern global public health challenge. airway is primary target in severe acute respiratory distress syndrome 2 (SARS-CoV-2) infection, with substantial cell death and lung injury being signature hallmarks exposure. viral factors that contribute to remain incompletely understood. Thus, this study investigated role open reading frame 7b (Orf7b), an accessory protein virus, causing injury. In screening proteins, we...
Abstract Background Early antibiotic exposure may disrupt gut microbiome and affect the gut-lung axis. We examined impact of prolonged during early life on growth subsequent acute lung injury (ALI) in a rat pup model. Methods Thirty-four 7-day-old pups were divided into Control, Antibiotics (Anti), Lung (LI), Antibiotics-Lung Injury (Anti-LI) groups. The Anti Anti-LI groups received oral Amoxicillin-Clavulanic acid from 7 to 40 days old, while Control LI sham water. ALI was induced with...
The enzyme acyl-CoA:lysophosphatidylcholine acyltransferase (Lpcat1) is a critical cytosolic needed for lung surfactant synthesis that catalyzes an reaction by adding palmitate to the sn-2 position of lysophospholipids. Here we report histone H4 protein subject palmitoylation catalyzed Lpcat1 in calcium-regulated manner. Cytosolic was observed shift into nucleus epithelia response exogenous Ca(2+). Nuclear colocalizes with and binds H4, where it palmitoylation. Mutagenesis studies...
Rac1, a member of the Rho family GTPases, regulates diverse cellular functions, including cytoskeleton reorganization and cell migration. F-box proteins are major subunits within Skp1-Cul1-F-box (SCF) E3 ubiquitin ligases that recognize specific substrates for ubiquitination. The role in regulating Rac1 stability has not been studied. Mouse lung epithelial (MLE12) cells were used to investigate Screening an protein library vitro ubiquitination assays identified FBXL19, relatively new targets...
Abstract Cytokine-driven inflammation underlies the pathobiology of a wide array infectious and immune-related disorders. The TNFR-associated factor (TRAF) proteins have vital role in innate immunity by conveying signals from cell surface receptors to elicit transcriptional activation genes encoding proinflammatory cytokines. We discovered that ubiquitin E3 ligase F box component, termed Fbxo3, potently stimulates cytokine secretion human inflammatory cells mediating degradation TRAF...
The HGF gene is transcriptionally silenced in normal differentiated breast epithelial cells, but its repression fails to occur mammary carcinoma tissues and cell lines. molecular mechanisms underpinning aberrant expression cancer cells are unknown. Here we report the discovery of a DNA element located 750 bp upstream from transcription start site human promoter that acts as transcriptional repressor target deletion mutagenesis tissues. This consists mononucleotide repeat 30 deoxyadenosines...
Acute lung injury (ALI) is linked to mitochondrial injury, resulting in impaired cellular oxygen utilization; however, it unknown how these events are on the molecular level. Cardiolipin, a mitochondrial-specific lipid, generated by cardiolipin synthase (CLS1). Here, we show that S. aureus activates ubiquitin E3 ligase component, Fbxo15, sufficient mediate proteasomal degradation of CLS1 epithelia, decreased availability and disrupted function. destabilized phosphatase tensin homolog...
Whole lung tissue transcriptomic profiling studies in chronic obstructive pulmonary disease (COPD) have led to the identification of several genes associated with severity airflow limitation and/or presence emphysema, however, cell types driving these gene expression signatures remain unidentified.To determine specific changes severe COPD, we conducted single-cell RNA sequencing (scRNA seq) on n = 29,961 cells from peripheral parenchymal nonsmoking subjects without underlying (n 3) and...
Abstract Fbxl7, a subunit of the SCF (Skp-Cul1-F-box protein) complex induces mitotic arrest in cells; however, molecular factors that control its cellular abundance remain largely unknown. Here, we identified an orphan F-box protein, Fbxl18, targets Fbxl7 for polyubiquitylation and proteasomal degradation. Lys 109 within is essential acceptor site ubiquitin conjugation by Fbxl18. An FQ motif serves as recognition Fbxl18 interaction. Ectopically expressed apoptosis Hela cells, effect...
Acyl-CoA:lysophosphatidylcholine acyltransferase 1 (LPCAT1) is a relatively newly described and yet indispensable enzyme needed for generation of the bioactive surfactant phospholipid, dipalmitoylphosphatidylcholine (DPPtdCho). Here, we show that lipopolysaccharide (LPS) causes LPCAT1 degradation using Skp1-Cullin-F-box ubiquitin E3 ligase component, β-transducin repeat-containing protein (β-TrCP), polyubiquitinates LPCAT1, thereby targeting proteasomal degradation. was identified as...
Unchecked epithelial cell death is fundamental to the pathogenesis of pneumonia. The recognition unique signaling pathways that preserve viability may present new opportunities for interventional strategies. We describe mortality factor 4 like 1 (Morf4l1), a protein involved in chromatin remodeling, constitutively expressed at low levels lung because its continuous degradation mediated by an orphan ubiquitin E3 ligase subunit, Fbxl18. Expression Morf4l1 increases humans with pneumonia and...
Because of the serious side effects currently used bronchodilators, new compounds with similar functions must be developed. We screened several herbs and found that Polygonum aviculare L. contains ingredients inhibit precontraction mouse human airway smooth muscle (ASM). High K+-induced in ASM was completely inhibited by nifedipine, a selective blocker L-type voltage-dependent Ca2+ channels (LVDCCs). However, nifedipine only partially reduced induced acetylcholine chloride (ACH)....
E3 ubiquitin ligase recognizes its protein substrates via specific molecular signatures for proteasomal degradation. However, the role of acetylation/deacetylation in process recognizing is not fully studied. Here, we report that a tandem IK motif arginine methyltransferase 1 (PRMT1) forms an acetyldegron to recruit F-box/LRR-repeat 17 (FBXL17), component SKP1-CUL1-F-box (SCF)-type complex. PRMT1 polyubiquitylated proteasome degradation with half-life approximately 4 h lung epithelial cells....
The Skp-Cul-F box (SCF) ubiquitin E3 ligase machinery recognizes predominantly phosphodegrons or, less commonly, an (I/L)Q molecular signature within substrates to facilitate their recruitment in mediating protein ubiquitination and degradation. Here, we examined the signals that determine turnover of multifunctional enzyme nucleoside diphosphate kinase A (NDPK-A) controls cell proliferation. NDPK-A exhibits a half-life ∼6 h HeLa cells is targeted for ubiquitylation through actions F-box...
Cortex phellodendri is used to reduce fever and remove dampness toxin. Berberine an active ingredient of C. . from Argemone ochroleuca can relax airway smooth muscle (ASM); however, whether the nonberberine component has similar relaxant action was unclear. An n‐butyl alcohol extract (NBAECP, component) prepared, which completely inhibits high K + ‐ acetylcholine‐ (ACH‐) induced precontraction in tracheal rings lung slices control asthmatic mice, respectively. The contraction by also blocked...