A5108050916- Muscle Physiology and Disorders
- Advanced Fluorescence Microscopy Techniques
- Neurogenetic and Muscular Disorders Research
- Signaling Pathways in Disease
- Spectroscopy Techniques in Biomedical and Chemical Research
- RNA Research and Splicing
- RNA modifications and cancer
- Adipose Tissue and Metabolism
- Exercise and Physiological Responses
- Melanoma and MAPK Pathways
- Cytokine Signaling Pathways and Interactions
- Optical Coherence Tomography Applications
- NF-κB Signaling Pathways
- Optical Imaging and Spectroscopy Techniques
- Telomeres, Telomerase, and Senescence
- Photoacoustic and Ultrasonic Imaging
- Ubiquitin and proteasome pathways
- Protein Tyrosine Phosphatases
- Microtubule and mitosis dynamics
- Histone Deacetylase Inhibitors Research
- Cancer-related Molecular Pathways
- PI3K/AKT/mTOR signaling in cancer
- Tissue Engineering and Regenerative Medicine
- Genomics and Chromatin Dynamics
- Viral-associated cancers and disorders
University of Hong Kong
2015-2024
Hong Kong University of Science and Technology
2015-2024
University of British Columbia
2015-2024
Chinese University of Hong Kong
2023-2024
The University of Tokyo
2020-2024
Hong Kong Polytechnic University
2023-2024
Max Planck Institute for Biology
2024
Vancouver Coastal Health
2017-2024
Vancouver Coastal Health Research Institute
2017-2024
Zhejiang University
2024
The extracellular signals which regulate the myogenic program are transduced to nucleus by mitogen-activated protein kinases (MAPKs). We have investigated role of two MAPKs, p38 and signal-regulated kinase (ERK), whose activities undergo significant changes during muscle differentiation. is rapidly activated in myocytes induced differentiate. This activation differs from those triggered stress cytokines, because it not linked Jun–N-terminal stimulation maintained whole process myotube...
Signaling pathways that stabilize interleukin-2 (IL-2) messenger RNA (mRNA) in activated T cells were examined. IL-2 mRNA contains at least two cis elements mediated its stabilization response to different signals, including activation of c-Jun amino-terminal kinase (JNK). This was through a element encompassing the 5' untranslated region (UTR) and beginning coding region. transcripts lacking this no longer responded JNK but still responsive other signals generated during cell activation,...
There is currently no optimal treatment or effective drug for severe acute respiratory syndrome (SARS), because the immunopathologic mechanism poorly understood.To explore immune underlying pathogenesis of SARS, we studied expression profile cytokines/chemokines in blood and immunopathology lung lymphoid tissues.Fourteen 23 patients with SARS were dynamically screened, using a bead-based multiassay system. Reverse transcription-polymerase chain reaction was performed to amplify mRNA....
MyoD inhibits cell proliferation and promotes muscle differentiation. A paradoxical feature of rhabdomyosarcoma (RMS), a tumor arising from precursors, is the block differentiation program deregulated despite expression. deficiency in RMS factor required for activity has been implicated by previous studies. We report here that p38 MAP kinase (MAPK) activation, which essential differentiation, deficient cells. Enforced induction MAPK an activated 6 (MKK6EE) restored function enhanced MEF2...
Myostatin is a transforming growth factor beta superfamily member and known as an inhibitor of skeletal muscle cell proliferation differentiation. Exposure to myostatin induces G1 phase cycle arrest. In this study, we demonstrated that down-regulates Cdk4 activity via promotion cyclin D1 degradation. Overexpression significantly blocked myostatin-induced inhibition. We further showed phosphorylation at threonine 286 by GSK-3beta was required for myostatin-stimulated nuclear export This...
MAP kinase (MAPK) cascades are composed of a MAPK, MAPK (MAPKK), and MAPKK (MAPKKK). Despite the existence numerous components ample opportunities for crosstalk, most MAPKs specifically distinctly activated. We investigated basis specific activation JNK subgroup MAPKs. The specificity is determined by JNKK1, which interacts with MAPKKK MEKK1 through its amino-terminal extension. Inactive JNKK1 mutants can disrupt or tumor necrosis factor (TNF) in intact cells only if they contain an...
Skeletal muscle stem cell–derived myoblasts are mainly responsible for postnatal growth and injury-induced regeneration. However, the cellular signaling pathways controlling proliferation differentiation of not fully understood. We demonstrate that Janus kinase 1 (JAK1) is required myoblast it also functions as a checkpoint to prevent from premature differentiation. Deliberate knockdown JAK1 in both primary immortalized induces precocious myogenic with concomitant reduction cell...
Skeletal muscle satellite cell-derived myoblasts are mainly responsible for postnatal growth and injury-induced regeneration. However, the cellular signaling pathways that control proliferation differentiation of remain poorly defined. Recently, we found JAK1/STAT1/STAT3 not only participate in myoblast but also actively prevent them from premature differentiation. Unexpectedly, a related pathway consisting JAK2, STAT2, STAT3 is required early myogenic Interference this by either small...
One of the pathological hallmarks Alzheimer's disease (AD) is deposition extracellular amyloid-β (Aβ) peptide, which generated from cleavage amyloid precursor protein (APP). Accumulation Aβ thought to associate with progressive neuronal death observed in AD. However, precise signaling mechanisms underlying action AD pathophysiology are not completely understood. Here, we report involvement transcription factor signal transducer and activator 3 (STAT3) mediating Aβ-induced death. We find that...
Abstract Malat1 is one of the most abundant long non-coding RNAs in various cell types; its exact cellular function still a matter intense investigation. In this study we characterized skeletal muscle cells and regeneration. Utilizing both vitro vivo assays, demonstrate that has role regulating gene expression during myogenic differentiation myoblast cells. Specifically, found knockdown accelerates cultured Consistently, knockout mice display enhanced regeneration after injury deletion...
Little is known about three-dimensional (3D) genome organization in skeletal muscle stem cells [also called satellite (SCs)]. Here, we comprehensively map the 3D topology reorganization during mouse SC lineage progression. Specifically, rewiring at compartment level most pronounced when SCs become activated. Marked loss topologically associating domain (TAD) border insulation and chromatin looping also occurs early activation process. Meanwhile, TADs can form TAD clusters...
Insulin-like growth factors (IGFs) can stimulate skeletal muscle differentiation. One of the molecular mechanisms underlying IGF-stimulated myogenesis is transcriptional induction myogenin. The current work aimed to elucidate signaling pathways mediating IGF effect on myogenin promoter in mouse C2C12 myogenic cells. We show that phosphatidylinositol 3-kinase (PI3K)/Akt and p70 S6K are crucial molecules stimulatory IGFs expression. have identified three cis-elements, namely E box, MEF2, MEF3...
A eukaryotic protein is often subject to regulation by multiple modifications like phosphorylation, acetylation, ubiquitination, and sumoylation. How these are coordinated in vivo an important issue that poorly understood but relevant many biological processes. We recently showed human MEF2D (myocyte enhancer factor 2D) sumoylated on Lys-439. Adjacent the sumoylation motif Ser-444, which Lys-439 highly conserved among MEF2 proteins from diverse species. Here we present [corrected] several...
Myocyte enhancer factor 2 (MEF2) family proteins are key transcription factors controlling gene expression in myocytes, lymphocytes, and neurons. MEF2 known to be regulated by phosphorylation. We now provide evidence showing that MEF2C is acetylated p300 both vitro vivo. In C2C12 myogenic cells, preferentially differentiating myocytes but not undifferentiated myoblasts. Several major acetylation sites mapped the transactivation domain of MEF2C, some which fully conserved other members from...
Amplification of 1q21 is the most frequent genetic alteration in human hepatocellular carcinoma (HCC), being detected 58%-78% primary HCC cases by comparative genomic hybridization. Recently, we isolated a candidate oncogene, Amplified Liver Cancer 1 (ALC1), from hybrid selection. Here demonstrate that ALC1 was frequently amplified and overexpressed HCC. ALC1-transfected cells possessed strong oncogenic ability, increasing colony formation soft agar tumorigenicity nude mice, which could be...
Nasopharyngeal carcinoma (NPC) is a common disease in Hong Kong and southern provinces of China. EBV infection believed to play critical role the development NPC. Previous studies on transformation mechanism genes were mostly performed either NPC or nonnasopharyngeal epithelial cells which may not be representative premalignant nasopharyngeal cells. Establishment cell system would greatly facilitate elucidation Using telomerase alone, we able establish an immortalized line from primary...
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma found in children and young adults. It characterized by expression of a number skeletal muscle-specific proteins, including MyoD muscle α-actin. However, unlike normal myoblasts, RMS cells differentiate poorly both vivo culture. As microRNAs are known to regulate tumorigenesis, intensive efforts have been made identify that involved development. In this work, we miR-203 was frequently down-regulated promoter hypermethylation cell...
Epithelial ovarian cancer (EOC) has the highest mortality rate among gynecological malignancies owing to poor screening methods, non-specific symptoms and limited knowledge of cellular targets that contribute disease. Cyclin G2 is an unconventional cyclin acts oppose cell cycle progression. Dysregulation gene (CCNG2) in a variety human cancers been reported; however, role tumorigenesis remains unclear. In this study, we investigated function EOC. vitro vivo studies using several EOC-derived...
In a yeast two-hybrid screen using the full-length Akt as bait, we found that prohibitin 2 (PHB2) specifically interacts with Akt. The C terminus of (amino acids 413-480) and central region PHB2 120-232) are responsible for their mutual interaction. acts transcriptional repressor in cells. both MyoD MEF2, represses MyoD- MEF2-dependent gene transcription. Furthermore, binding to MEF2 significantly decreases upon myogenic differentiation. When stably expressed C2C12 cells, inhibits myogenin...
The tumor suppressor protein p53 is known to undergo cytoplasmic dynein-dependent nuclear translocation in response DNA damage. However, the molecular link between and minus end-directed microtubule motor dynein complex has not been described. We report here that 8-kDa light chain (LC8) of binds p53-binding 1 (53BP1). LC8-binding domain was mapped a short peptide segment immediately N-terminal kinetochore localization region 53BP1. completely separated from Therefore, 53BP1 can potentially...
AbstractAt least three mitogen-activated protein kinase (MAPK) cascades were identified in mammals, each consisting of a well-defined three-kinase module composed MAPK, MAPK (MAPKK), and MAPKK (MAPKKK). These play key roles relaying various physiological, environmental, or pathological signals from the environment to transcriptional machinery nucleus. One these MAPKs, c-Jun N-terminal (JNK), stimulates activity response growth factors, proinflammatory cytokines, certain environmental...