A5072557821- Ubiquitin and proteasome pathways
- Histone Deacetylase Inhibitors Research
- Biochemical and Structural Characterization
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Peptidase Inhibition and Analysis
- Protein Kinase Regulation and GTPase Signaling
- Click Chemistry and Applications
- Protein Degradation and Inhibitors
- Chemical Synthesis and Analysis
- Hearing, Cochlea, Tinnitus, Genetics
- Food Allergy and Anaphylaxis Research
- Cancer-related gene regulation
- Lymphoma Diagnosis and Treatment
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- Mycotoxins in Agriculture and Food
- Hearing Loss and Rehabilitation
- Cancer-related Molecular Pathways
- Allergic Rhinitis and Sensitization
- Plant Gene Expression Analysis
- Photosynthetic Processes and Mechanisms
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Plant biochemistry and biosynthesis
- Advanced Proteomics Techniques and Applications
Westlake University
2020-2025
Jimei University
2024-2025
Institute of Natural Science
2025
Institute for Advanced Study
2025
Qingdao University
2020-2024
Harvard University
2018-2024
Affiliated Hospital of Qingdao University
2020-2024
Brigham and Women's Hospital
2018-2024
Eye & ENT Hospital of Fudan University
2021-2023
State Key Laboratory of Medical Neurobiology
2021-2023
Abstract Here we report corin, a synthetic hybrid agent derived from the class I HDAC inhibitor (entinostat) and an LSD1 (tranylcypromine analog). Enzymologic analysis reveals that corin potently targets CoREST complex shows more sustained inhibition of activity compared with entinostat. Cell-based experiments demonstrate exhibits superior anti-proliferative profile against several melanoma lines cutaneous squamous cell carcinoma to its parent monofunctional inhibitors but is less toxic...
The transcriptional corepressor complex CoREST is one of seven histone deacetylase complexes that regulate the genome through controlling chromatin acetylation. unique in containing both demethylase and enzymes, LSD1 HDAC1, held together by RCOR1 scaffold protein. To date, it has been assumed enzymes function independently within complex. Now, we report assembly ternary Using structural functional studies, show activity two closely coupled can exist at least distinct states with different...
Significance Inositol polyphosphates and pyrophosphates are ubiquitous eukaryotic messengers involved in numerous cellular processes, including insulin signaling cell migration. Nevertheless, annotation of the specific events underlying these processes has been stymied by lack suitable tools. By applying chemically synthesized affinity reagents, we comprehensively annotated inositol polyphosphate binding proteins model organism Saccharomyces cerevisiae , revealing a role for molecules...
We describe a new method to produce histone H2B by semisynthesis with an engineered sortase transpeptidase. N-Terminal tail site-specifically modified acetylated, lactylated, and β-hydroxybutyrylated H2Bs were incorporated into nucleosomes investigated as substrates of deacetylase (HDAC) complexes sirtuins. A wide range rates site-specificities observed these enzyme forms suggesting distinct biological roles in regulating chromatin structure epigenetics.
The mechanical cues of the external microenvironment have been recognized as essential clues driving cell behavior. Although intracellular signals modulating fate during sensory epithelium development is well understood, force formation remains elusive. Here, we manufactured a hybrid hydrogel with tunable properties for cochlear organoids culture and revealed that extracellular matrix (ECM) drives through shifting stiffness in stage-dependent pattern. As force, moderate ECM activated...
Inositol pyrophosphates, such as diphosphoinositol pentakisphosphate (IP7), are conserved eukaryotic signaling molecules that possess pyrophosphate and monophosphate moieties. Generated predominantly by inositol hexakisphosphate kinases (IP6Ks), pyrophosphates can modulate protein function posttranslational serine pyrophosphorylation. Here, we report novel regulators of cytoplasmic dynein-driven vesicle transport. Mammalian cells lacking IP6K1 display defects in dynein-dependent trafficking...
Inositol pyrophosphates are high energy signaling molecules involved in cellular processes, such as energetic metabolism, telomere maintenance, stress responses, and vesicle trafficking, can mediate protein phosphorylation. Although the inositol kinases underlying pyrophosphate biosynthesis well characterized, phosphatases that selectively regulate their pools not fully described. The diphosphoinositol phosphate phosphohydrolase enzymes of Nudix family have been demonstrated to...
Histone acetylation regulates chromatin structure and gene expression is removed by histone deacetylases (HDACs). HDACs are commonly found in various protein complexes to confer distinct cellular functions, but how the multi-subunit influence deacetylase activities site-selectivities poorly understood. Previously we reported results of studies on HDAC1 containing CoREST complex acetylated nucleosome substrates which revealed a notable preference for deacetylation H3 acetyl-Lys9 vs....
A gene cluster (pol) essential for the biosynthesis of polyoxin, a nucleoside antibiotic widely used control phytopathogenic fungi, was cloned from Streptomyces cacaoi. 46,066-bp region sequenced, and 20 39 putative open reading frames were defined as necessary polyoxin evidenced by its production in heterologous host, lividans TK24. The role PolO PolA synthesis demonstrated vivo experiments, their functions unambiguously characterized O-carbamoyltransferase UMP-enolpyruvyltransferase,...
The diphosphoinositol polyphosphates (PP-IPs) are a central group of eukaryotic second messengers. They regulate numerous processes, including cellular energy homeostasis and adaptation to environmental stresses. To date, most the molecular details in PP-IP signalling have remained elusive, due lack appropriate methods reagents. Here we describe expedient synthesis methylene-bisphosphonate analogues. Their characterization revealed that analogues exhibit significant stability mimic their...
The core CoREST complex (LHC) contains histone deacetylase HDAC1 and demethylase LSD1 held together by the scaffold protein CoREST. Here, we analyze purified LHC with modified peptide reconstituted semisynthetic mononucleosome substrates. activity toward methyl-Lys4 in H3 is strongly inhibited Lys14 acetylation, this appears to be an intrinsic property of subunit. Moreover, selectivity unexpectedly shows a marked preference for acetyl-Lys9 versus acetyl-Lys14 nucleosome substrates but lost...
After long-term clinical application, traditional Chinese medicine (TCM) has accumulated rich experience in the stroke treatment. Huang-Qi-Long-Dan Granule (HQLDG) is a TCM formula that been used for treatment of acute ischemic stroke. However, its mechanism against still unknown. This study aimed to identify HQLDG's effect and explore underlying mechanism. 16s rRNA sequencing, metabolomics/tryptophan (Trp)-targeted metabolomics analysis transcriptomic were investigate HQLDG therapeutic Our...
Abstract The diphosphoinositol polyphosphates (PP‐IPs) represent a novel class of high‐energy phosphate‐containing messengers which control wide variety cellular processes. It is thought that PP‐IPs exert their pleiotropic effects as allosteric regulators and through pyrophosphorylation protein substrates. However, most details PP‐IP signaling have remained elusive because paucity suitable tools. We describe the synthesis bisphosphonate analogues (PCP‐IPs), are resistant to chemical...
p300 and CBP are highly related histone acetyltransferase (HAT) enzymes that regulate gene expression, their dysregulation has been linked to cancer other diseases. p300/CBP is composed of a number domains including HAT domain, which inhibited by the small molecule A-485, an acetyl-lysine binding bromodomain, was recently found be selectively antagonized I-CBP112. Here we show combination I-CBP112 A-485 can synergize inhibit prostate cell proliferation. We find confers dramatic reduction in...
Salvia species have been widely used as medicinal plants and played an important role in the treatment recovery of individuals with COVID-19. In this study, we reported two newly identified whole chloroplast genome sequences (S. yangii S. miltiorrhiza f. alba) compared them those seven other genomes; these proved to be highly similar terms overall size, structure, gene content, order. We ten mutation hotspots (trnK-rps16, atpH-atpI, psaA-ycf3, ndhC-trnV, ndhF, rpl32-trnL, ndhG-ndhI,...
Functional cochlear hair cells (HCs) innervated by spiral ganglion neurons (SGNs) are essential for hearing, whereas robust models that recapitulate the peripheral auditory circuity still lacking. Here, we developed organoids with functional in a staging three-dimensional (3D) co-culture system initially reprogramming progenitor (CPCs) increased proliferative potency could be long-term expanded, then stepwise inducing differentiation of HCs, as well outgrowth neurites from SGNs. The function...
Tropomyosin was reported as an important allergen in Crassostrea angulata and designated Cra a 1. The localization of the T cell epitopes reduction immunoreactivity 1 are still lacking. In this study, four were identified by using wild-type (wtCra 1)-immunized mouse splenocytes cultured with synthetic peptides. maintained after chemical denaturation treatment, indicating that linear epitope is immunodominant wtCra Furthermore, hypoallergenic derivative (mCra 1) developed deletion B retention...
Sarcoplasmic calcium-binding protein identified in Crassostrea angulata (Cra a 4), is stable allergen; the methods to reduce its allergenicity are still limited. The present study aimed develop hypoallergenic enzymatic hydrolyzate of Cra 4 (ECra 4) by enzymolysis. After screening proteases bioinformatics and optimization enzymolysis conditions, ECra was obtained with Trypsin. Further, used stimulate splenocytes from 4-sensitized mice, findings that could CD4+ T-cell proliferation, inhibit...
Protein phosphorylation is a very important post-translational modification that regulates diverse cellular activities. In addition to classic monophosphorylation, there also oligophosphorylation from pyrophosphorylation polyphosphorylation. Moreover, organophosphates may modify residues such as via AMPylation and ADPylation. Although plenty of new types protein have been revealed, molecular mechanisms the biological functions are still challenging study due lack good method prepare proteins...