A5075826891- Ubiquitin and proteasome pathways
- Advanced Proteomics Techniques and Applications
- Generative Adversarial Networks and Image Synthesis
- RNA modifications and cancer
- Pharmacological Receptor Mechanisms and Effects
- Protein Tyrosine Phosphatases
- Tryptophan and brain disorders
- Galectins and Cancer Biology
- Glycosylation and Glycoproteins Research
- Cellular transport and secretion
- Autophagy in Disease and Therapy
- Mass Spectrometry Techniques and Applications
- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
- Microfluidic and Capillary Electrophoresis Applications
- Electrochemical sensors and biosensors
- Electrochemical Analysis and Applications
- Invertebrate Immune Response Mechanisms
- Peptidase Inhibition and Analysis
- Biochemical Acid Research Studies
- Anomaly Detection Techniques and Applications
- Analytical Chemistry and Chromatography
- Music and Audio Processing
- Cancer therapeutics and mechanisms
- Topic Modeling
Academia Sinica
2003-2025
National Health Research Institutes
2014-2024
Institute of Biological Chemistry, Academia Sinica
2014-2024
National Central University
2024
Harbin Institute of Technology
2024
Chang Jung Christian University
2023
South China University of Technology
2023
University of Oxford
2018-2022
National Yang Ming Chiao Tung University
2010-2021
Chengdu University of Information Technology
2021
Activation of tumor suppressors for the treatment human cancer has been a long sought, yet elusive, strategy. PTEN is critical suppressive phosphatase that active in its dimer configuration at plasma membrane. Polyubiquitination by ubiquitin E3 ligase WWP1 (WW domain-containing 1) suppressed dimerization, membrane recruitment, and function PTEN. Either genetic ablation or pharmacological inhibition triggered reactivation unleashed activity. appears to be direct MYC (MYC proto-oncogene)...
MicroRNAs (miRNA) mediate distinct gene regulatory pathways triggered by epidermal growth factor receptor (EGFR) activation, which occurs commonly in lung cancers with poor prognosis. In this study, we report the discovery and mechanistic characterization of miRNA miR-7 as an oncogenic "oncomiR" its role a key mediator EGFR signaling cancer cells. activation or ectopic expression Ras well c-Myc stimulated extracellular signal-regulated kinase (ERK)-dependent manner, suggesting that induces...
In this work, we propose a VAE-LSTM hybrid model as an unsupervised approach for anomaly detection in time series. Our utilizes both VAE module forming robust local features over short windows and LSTM estimating the long term correlation series on top of inferred from module. As result, our algorithm is capable identifying anomalies that span multiple scales. We demonstrate effectiveness five real world problems find method outperforms three other commonly used methods.
Proteomic analysis of sera and the quest for identifying serum proteins as disease markers have often been hampered by predominance several highly abundant including albumin immunoglobulins. Prior depletion so to enrich otherwise undetectable components is therefore a prerequisite in mining proteome. In course evaluating available methods commercial kits, we able refine protocols establish modified removal method using trichloroacetic acid (TCA)/acetone. Changes major protein bands were...
In this study, we used a systems biology approach to investigate changes in the proteome and metabolome of shrimp hemocytes infected by invertebrate virus WSSV (white spot syndrome virus) at viral genome replication stage (12 hpi) late (24 hpi). At 12 hpi, but not 24 there was significant up-regulation markers several metabolic pathways associated with vertebrate Warburg effect (or aerobic glycolysis), including glycolysis, pentose phosphate pathway, nucleotide biosynthesis, glutaminolysis...
Indoleamine 2,3-dioxygenase 1 (IDO1), promoting immune escape of tumors, is a therapeutic target for the cancer immunotherapy. A number IDO1 inhibitors have been identified, but only limited structural biology studies are available to provide insights on binding mechanism IDO1. In this study, we present structure in complex with 24, NLG919 analogue potent activity. The revealed imidazole nitrogen atom 24 coordinate heme iron, and imidazoleisoindole core situated pocket 1-cyclohexylethanol...
Significance As autotrophic organisms, sugar status in plants must be constantly monitored and reacted to order maintain homeostatic states crucial for growth regulation, environmental stress tolerance, productivity. α-Amylase (αAmy) is the key enzyme hydrolyzing starch into sugars regulated by levels; it induced starvation but repressed provision. Two MYBs compete binding same αAmy promoter element regulate this process, with MYBS1 promoting MYBS2 repressing expression. Induction of...
Abstract The ubiquitin–proteasome system (UPS) and autophagy are two major quality control processes whose impairment is linked to a wide variety of diseases. coordination between UPS remains incompletely understood. Here, we show that ubiquitin ligase UBE3C deubiquitinating enzyme TRABID reciprocally regulate K29/K48-branched ubiquitination VPS34. We find this enhances the binding VPS34 proteasomes for degradation, thereby suppressing autophagosome formation maturation. Under ER proteotoxic...
Excessive generation and accumulation of highly reactive oxidizing molecules causes oxidative stress damage to cellular components. Accumulating evidence indicates that autophagy diminishes in cells maintains redox homeostasis by degrading recycling intracellular damaged Here, we show TRAF6 E3 ubiquitin ligase A20 deubiquitinase coordinate regulate ATG9A ubiquitination activation responding stress. The ROS-dependent TRAF6-mediated non-proteolytic, K48/63-linked enhances its association with...
Arsenite was shown to inhibit pyruvate dehydrogenase (PDH) activity through binding vicinal dithiols in pure enzyme and tissue extract. However, no data are available on how arsenite inhibits PDH human cells. The IC50 values for arsenic trioxide (As2O3) the porcine heart preparation leukemia cell line HL60 cells were estimated be 182 2 μM, respectively. Thus, As2O3 inactivation of about 90 times more potent than purified preparation. phenylarsine oxide reduce thiol content 81.7 1.9 is a...
Encapsulated Klebsiella pneumoniae is the predominant causative agent of pyogenic liver abscess, an emerging infectious disease that often complicates metastatic meningitis or endophthalmitis. The capsular polysaccharide on K. surface was determined as key to virulence. Although regulation biosynthesis largely unclear, it found protein-tyrosine kinases and phosphatases are involved. Therefore, identification characterization such kinases, phosphatases, their substrates would advance our...
Tryptophan metabolism has been recognized as an important mechanism in immune tolerance. Indoleamine 2,3-dioxygenase plays a key role local tryptophan via the kynurenine pathway and emerged therapeutic target for cancer immunotherapy. Our prior study identified phenyl benzenesulfonyl hydrazide 2 potent vitro (though not vivo) inhibitor of indoleamine 2,3-dioxygenase. Further lead optimization to improve potencies pharmacokinetic profiles resulted...
Protein post-translational modifications (PTMs) are crucial in plant cellular processes, particularly protein folding and signal transduction. N-glycosylation phosphorylation notably significant PTMs, playing essential roles regulating responses to environmental stimuli. However, current sequential enrichment methods for simultaneous analysis of phosphoproteome N-glycoproteome labor-intensive time-consuming, limiting their throughput. Addressing this challenge, study introduces a novel...
Significance Vasopressin is a peptide hormone that regulates renal water excretion to maintain whole-body balance. It does so by regulating trafficking of molecular channel, aquaporin-2, and from the plasma membrane collecting duct cells. This study uses two state-of-the-art methods (protein mass spectrometry affinity-isolated apical proteins live-cell imaging actin dynamics) uncover central role dynamics in aquaporin-2–containing vesicles. The results coupled with prior data produce model...
A structure-based virtual screening strategy, comprising homology modeling, ligand–support binding site optimization, screening, and structure clustering analysis, was developed used to identify novel tryptophan 2,3-dioxygenase (TDO) inhibitors. Compound 1 (IC50 = 711 nM), selected by showed inhibitory activity toward TDO subjected structural modifications molecular docking studies. This resulted in the identification of a potent selective inhibitor (11e, IC50 30 making it potential compound...
Protein deubiquitination contributes to cortical development, and its dysregulation is linked intellectual disability.
Plant phosphoproteomics provides a global view of phosphorylation-mediated signaling in plants; however, it demands high-throughput methods with sensitive detection and accurate quantification. Despite the widespread use protein precipitation for removing contaminants improving sample purity, limits sensitivity throughput plant phosphoproteomic analysis. The multiple handling steps involved lead to loss process variability. Herein, we developed an approach based on suspension trapping...
Abstract Ionospheric total electron content (TEC) is a key indicator of the space environment. Geophysical forcing from above and below drives its spatial temporal variations. A full understanding physical chemical principles, available well‐representable driving inputs, capable computational power are required for models to reproduce simulations that agree with observations, which may be challenging at times. Recently, data‐driven approaches, such as deep learning, have therefore surged...
Beyond the canonical K48-linked homotypic polyubiquitination for proteasome-targeted proteolysis, K11/K48-branched ubiquitin (Ub) chains are involved in fast-tracking protein turnover during cell cycle progression and proteotoxic stress. Here, we report cryo-EM structures of human 26S proteasome a complex with Ub chain. The revealed multivalent substrate recognition mechanism involving hitherto unknown K11-linked binding site at groove formed by RPN2 RPN10 addition to K48-linkage RPT4/5...