A5045911164- Biochemical and Molecular Research
- Developmental Biology and Gene Regulation
- Glycosylation and Glycoproteins Research
- Neurobiology and Insect Physiology Research
- Wnt/β-catenin signaling in development and cancer
- Immunotherapy and Immune Responses
- Carbohydrate Chemistry and Synthesis
- Cytomegalovirus and herpesvirus research
- Cancer Research and Treatments
- T-cell and B-cell Immunology
- Cellular Mechanics and Interactions
- Adenosine and Purinergic Signaling
- HIV/AIDS drug development and treatment
- RNA modifications and cancer
- Cellular transport and secretion
- Immune Cell Function and Interaction
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- interferon and immune responses
- Hippo pathway signaling and YAP/TAZ
- Silk-based biomaterials and applications
- Cytokine Signaling Pathways and Interactions
- Ubiquitin and proteasome pathways
- Signaling Pathways in Disease
- Protein Degradation and Inhibitors
Chang Gung University
2013-2023
Chang Gung Memorial Hospital
2015-2022
Princeton University
2000
Howard Hughes Medical Institute
2000
University of North Carolina at Chapel Hill
1993-1999
ABSTRACT Drosophila Armadillo and its vertebrate homolog β-catenin play essential roles both in the transduction of Wingless/Wnt cell-cell signals function adherens junctions. Wingless Wnts direct numerous cell fate choices during development. We generated a mutant protein, ArmadilloS10, with 54 amino acid deletion N-terminal domain. This is con-stitutively active signaling; activity inde-pendent signal endogenous wild-type Armadillo. Armadillo’s role normally negatively regulated by...
The essential metabolic enzyme CTP synthase (CTPsyn) can be compartmentalised to form an evolutionarily-conserved intracellular structure termed the cytoophidium. Recently, it has been demonstrated that enzymatic activity of CTPsyn is attenuated by incorporation into cytoophidia in bacteria and yeast cells. Here we demonstrate regulated a similar manner Drosophila tissues vivo. We show cytoophidium formation occurs during nutrient deprivation cultured cells, as well quiescent starved...
Cytidine triphosphate synthase (CTPS) and inosine monophosphate dehydrogenase (IMPDH) can form fiber-like subcellular structures termed “cytoophidia” under certain circumstances in mammalian cells. Although it has been shown that filamentation of CTPS downregulates its activity by disturbing conformational changes, the IMPDH within cytoophidia is still unclear. Most previous cytoophidium studies were done conditions involving inhibitors impair GTP synthesis. Here we show forms without...
Inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in de novo GTP biosynthesis, plays an important role cell metabolism and proliferation. It has been demonstrated that IMPDH can aggregate into a macrostructure, termed cytoophidium, mammalian cells under variety of conditions. However, regulation function cytoophidium are still elusive.In this study, we report spontaneous filamentation is correlated with rapid Intracellular IMP accumulation promoted assembly, whereas...
Adherens junctions are multiprotein complexes mediating cell-cell adhesion and communication. They organized around a transmembrane cadherin, which binds set of cytoplasmic proteins required for to link the complex actin cytoskeleton. Three components Drosophila adherens junctions, analogous those in vertebrates, have been identified: Armadillo (homolog beta-catenin), E-cadherin (DE-cadherin), alpha-catenin. We carried out first analysis interactions between these using vitro binding assays,...
Nonmuscle myosin II (NM-II) is an important motor protein involved in cell migration. Incorporation of NM-II into actin stress fiber provides a traction force to promote retrograde flow and focal adhesion assembly. However, the components regulation activity are not well understood. Here we identified novel fiber-associated protein, LIM calponin-homology domains 1 (LIMCH1), which regulates activity. The recruitment LIMCH1 contractile fibers revealed its localization complementary actinin-1....
Guanosine triphosphate (GTP) is a building block for DNA and RNA, plays pivotal role in various cellular functions, serving as an energy source, enzyme cofactor key component of signal transduction. The activity the rate‐limiting de novo GTP synthesis, inosine monophosphate dehydrogenase (IMPDH), regulated by nucleotide binding. Recent studies have illuminated that IMPDH octamers can assemble into linear polymers, adding another dimension to its enzymatic regulation. This polymerisation...
During infections and inflammation, plasmacytoid dendritic cells (pDCs) are the most potent type I interferon (IFN-I)–producing cells. However, developmental origin of pDCs signals dictating pDC generation remain incompletely understood. Here, we report a synergistic role for IFN-I Flt3 ligand (FL) in development from common lymphoid progenitors (CLPs). Both conventional DCs (cDCs) were generated CLPs response to FL, whereas required higher concentrations FL concurrent signaling. An absence...
Abstract CTP synthase (CTPsyn) plays an essential role in DNA, RNA, and lipid synthesis. Recent studies bacteria, yeast, Drosophila all reveal a polymeric CTPsyn structure, which dynamically regulates its enzymatic activity. However, the molecular mechanism underlying formation of polymers is not completely understood. In this study, we found that reversible ubiquitination dynamic assembly filamentous structures CTPsyn. We further determined proto-oncogene Cbl, E3 ubiquitin ligase, controls...
Abstract Altered glycosylations, which are associated with expression and activities of glycosyltransferases, can dramatically affect the function glycoproteins modify behavior tumor cells. ST3GAL1 is a sialyltransferase that adds sialic acid to core 1 glycans, thereby terminating glycan chain extension. In breast carcinomas, overexpression promotes tumorigenesis correlates increased grade. pursuing role in cancer using ST3GAL1-siRNA knockdown ST3GAL1, we identified CD55 be one potential...
Drosophila melanogaster Armadillo and its vertebrate homolog beta-catenin play multiple roles during development. Both are components of cell-cell adherens junctions both transduce Wingless (Wg)/Wnt intercellular signals. The current model for signaling proposes that binds the DNA-binding protein dTCF, forming a bipartite transcription factor activates Wingless-responsive genes. In this model, Armadillo's C-terminal domain is proposed to serve an essential role as transcriptional activation...
Cells must cooperate and communicate to form a multicellular animal. Information about the molecules required for these processes have come from variety of sources; convergence between studies particular by vertebrate cell biologists genes identified scientists investigating development in Drosophila has been especially fruitful. We are interested connection cadherin proteins that regulate cell-cell adhesion wingless/wnt-1 signaling controlling pattern formation during development. The...
The thyroid hormone 3,3',5-triiodo-L-thyronine (T(3)) regulates growth, development, and differentiation processes in animals. These activities are mediated by the nuclear receptors (TRs). Microarray analyses were performed previously to study mechanism of regulation triggered T(3) treatment hepatoma cell lines. results showed that spondin 2 was regulated positively T(3). However, underlying physiological role not clear. To verify microarray results, further investigated using...
CTP synthase (CTPS) forms compartmentalized filaments in response to substrate availability and environmental nutrient status. However, the physiological role of mechanisms for filament assembly are not well understood. Here, we provide evidence that CTPS histidine influx during glutamine starvation. Tetramer conformation-based formation restricts enzymatic activity deprivation. protein levels remain stable presence deprivation, followed by rapid cell growth after stress relief. We...
The asymmetric localization of gurken mRNA and post-translational sorting mechanisms are responsible for the polar distribution Gurken protein in Drosophila. However, endocytosis Egfr, receptor follicle cells, also plays a role shaping extracellular gradient morphogen. Previously, we have found that mutation Cbl gene caused elevated Egfr signaling along dorsoventral axis, resulted dorsalization phenotypes embryos egg shells. Here, report overexpression long isoform significantly changed...
The 5'-methylthioadenosine (MTA) cycle-participating human acireductone dioxygenase 1 (ADI1) has been implicated as a tumor suppressor in prostate cancer, yet its role remains unclear hepatocellular carcinoma (HCC). Here, we demonstrated significant reduction of ADI1, either protein or mRNA level, HCC tissues. Additionally, higher ADI1 levels were associated with favorable postoperative recurrence-free survival patients. By altering expression cells, negative correlation between and cell...
ABSTRACT Drosophila Armadillo and its vertebrate homolog β-catenin are key effectors of Wingless/Wnt signaling. In the current model, signal stabilizes Armadillo/β-catenin, which then accumulates in nuclei binds TCF/LEF family proteins, forming bipartite transcription factors activate responsive genes. This model was recently challenged. Overexpression Xenopus membrane-tethered or paralog plakoglobin activates Wnt signaling, suggesting that nuclear localization Armadillo/β-catenin is not...
Abstract Interferons (IFNs) are key regulators for both innate and adaptive immune responses. By screening ENU-mutagenized mice, we identified a pedigree- P117 which displayed impaired response to type I, but not II, IFNs. Through inheritance test, genetic mapping sequencing, found T A point mutation in the 5' splice site of STAT2 intron 4–5, leading cryptic splicing frame shifting. As result, expression protein was greatly diminished mutant mice. Nonetheless, trace amount functional still...
Living organisms respond to nutrient availability by regulating the activity of metabolic enzymes. Therefore, reversible post-translational modification an enzyme is a common regulatory mechanism for energy conservation. Recently, cytidine-5'-triphosphate (CTP) synthase was discovered form filamentous structure that evolutionarily conserved from flies humans. Interestingly, induction formation CTP filament responsive starvation or glutamine depletion. However, biological roles this remain...
Methionine, an essential amino acid, is required for protein synthesis and normal cell metabolism. The transmethylation pathway methionine salvage (MTA cycle) are two major pathways regulating Recently, has been reported to play a key role in Drosophila fecundity.Here, we revealed that the MTA cycle plays crucial fecundity using mutant of aci-reductone dioxygenase 1 (DADI1), enzyme cycle. In dietary restriction condition, egg production adi1 flies was reduced compared control flies. This...
ABSTRACT Under metabolic stress, cellular components can assemble into distinct membraneless organelles for adaptation. One such example is cytidine 5′-triphosphate synthase (CTPS, which there are CTPS1 and CTPS2 forms in mammals), filamentous structures under glutamine deprivation. We have previously demonstrated that histidine (His)-mediated methylation regulates the formation of CTPS filaments to suppress enzymatic activity preserve protein deprivation, promotes cancer cell growth after...
Proper control of Epidermal Growth Factor Receptor (EGFR) signaling is critical for normal development and regulated cell behaviors. Abnormal EGFR associated with tumorigenic process various cancers. Complicated feedback networks through ligand production, internalization-mediated destruction ligand-receptor complexes. Previously, we found that two isoforms D-Cbl, D-CblS D-CblL, regulate distinct mechanisms. While D-CblL plays a crucial role in dose-dependent down-regulation signaling, acts...