A5019178313- Fungal and yeast genetics research
- Genomics and Rare Diseases
- Microtubule and mitosis dynamics
- Wnt/β-catenin signaling in development and cancer
- Cancer-related Molecular Pathways
- Protein Kinase Regulation and GTPase Signaling
- Plant Reproductive Biology
- 14-3-3 protein interactions
- Retinoids in leukemia and cellular processes
- Genomics and Chromatin Dynamics
- Ubiquitin and proteasome pathways
- BRCA gene mutations in cancer
- Blood Coagulation and Thrombosis Mechanisms
- Genomic variations and chromosomal abnormalities
- Polyamine Metabolism and Applications
- Pharmaceutical studies and practices
- interferon and immune responses
- Cell death mechanisms and regulation
- Cancer-related gene regulation
- RNA modifications and cancer
- S100 Proteins and Annexins
- Pharmaceutical Economics and Policy
- Endoplasmic Reticulum Stress and Disease
- MicroRNA in disease regulation
- Peroxisome Proliferator-Activated Receptors
Sun Yat-sen University
2024
The First Affiliated Hospital, Sun Yat-sen University
2024
Zhongshan Hospital
2024
Fudan University
2024
National Organization for Rare Disorders
2021
National Health Research Institutes
2021
National Institutes of Health
2021
National Bureau of Statistics of China
2021
The University of Texas MD Anderson Cancer Center
1996-2018
Shanghai Children's Medical Center
2011-2013
The promyelocytic leukemia gene (PML) involved in the t(15;17) (q22;q12) translocation acute is a growth suppressor. To elucidate functional domains of PML, several mutants lacking nuclear localization signal (PMLnls-), dimerization domain (PMLdim-), proline-rich at N-terminal (PMLpro-), RING finger motif (PMLpr-), B-box-1 (PMLprb-), serine-proline-rich C-terminal (PMLsp-), and double mutant (PMLprb-nls-) have been constructed. Immunofluorescence staining transiently transfected NIH3T3 cells...
In the evolutionarily distant yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, genetic evidence suggests that activation of pheromone-induced mitogen-activated protein kinase (MAPK) cascades involves function p21cdc42/racl-activated kinases (PAKs) Ste20 Shk1, respectively. this report, we show purified Shk1 were each capable inducing p42MAPK in cell-free extracts Xenopus laevis oocytes, while a mammalian Ste20/Shk1-related kinase, p65pak (Pak1), did not induce p42MAPK. contrast...
Abstract Background China has made tremendous progresses in serving the needs of its people living with rare diseases past decade, especially over last 5 years. The Chinese government’s systematic approach included a series coordinated initiatives, amongst these are: forming Rare Disease Expert Committee (2016), funding “Rare Diseases Cohort Study” (2016–2020), and publishing first Catalog” (2018). Herein, we present National Registry System (NRDRS)—China’s national registry, analysis cases...
AbstractThe histone proteins are essential for the assembly and function of eukaryotic chromosome. Here we report first isolation a temperature-sensitive lethal H4 mutant defective in mitotic chromosome transmission Saccharomyces cerevisiae. The requires two amino acid substitutions H4: Thr-to-Ile change at position 82, which lies within one DNA-binding surfaces protein, substitution Ala to Val 89 that is an intragenic suppressor. Genetic biochemical evidence shows temperature sensitive but...
We previously provided evidence that the protein encoded by highly conserved skb1 gene is a putative regulator of Shk1, p21 Cdc42/Rac -activated kinase (PAK) homolog in fission yeast Schizosaccharomyces pombe. null mutants are viable and competent for mating but less elongate than wild-type S. pombe cells, whereas cells overexpress hyperelongated. These phenotypes suggest possible role Skb1 as mitotic inhibitor. Here we show genetic interactions both shk1 with genes encoding key regulators ....
The Shk1 protein kinase, a homolog of Saccharomyces cerevisiae Ste20 and mammalian p21 Cdc42/Rac -activated kinases, is an essential component Ras- Cdc42-dependent signaling cascade required for cell viability, normal morphology, mitogen-activated kinase-mediated sexual responses in the fission yeast, Schizosaccharomyces pombe . To identify S. proteins that modulate or mediate functions, we conducted two-hybrid screen Shk1-interacting proteins. One genes identified as result this was skb1 We...
Cse4p is a structural component of the core centromere Saccharomyces cerevisiae and member conserved CENP-A family specialized histone H3 variants. The H4 allele hhf1-20 confers defects in chromatin structure mitotic chromosome transmission. We have proposed that interact through their respective fold domains to assemble nucleosome-like at centromeric DNA. To test this model, we targeted random mutations domain isolated three temperature-sensitive cse4 alleles an unbiased genetic screen. Two...
Phenylketonuria (PKU), an autosomal recessive disorder of amino acid metabolism caused by mutations in the phenylalanine hydroxylase (PAH) gene, leads to childhood mental retardation exposing neurons cytotoxic levels (Phe). A recent study showed that mitochondria-mediated (intrinsic) apoptotic pathway is involved Phe-induced apoptosis cultured cortical neurons, but it not known if death receptor (extrinsic) and endoplasmic reticulum (ER) stress-associated also contribute neurodegeneration...
The Ste20/p21-activated kinase homolog Shk1 is essential for viability and required normal morphology, mating, cell cycle control in the fission yeast Schizosaccharomyces pombe. regulated by p21 G protein Cdc42, which has been shown to form a complex with SH3 domain Scd2 (also called Ral3). In this study, we investigated whether plays role regulating function. We found that recombinant interact directly vitro they vivo, as determined two-hybrid assay genetic analyses yeast. second of two...
We describe the characterization of a novel gene,shk2, encoding second p21cdc42/rac-activated protein kinase (PAK) homolog in fission yeast. Like other known PAKs, Shk2 binds to Cdc42 vivo and vitro. While overexpression either shk2 or cdc42 alone does not impair growth wild type yeast cells, cooverexpression two genes is toxic leads highly aberrant cell morphology, providing evidence for functional interaction between proteins vivo. Fission yeastshk2 null mutants are viable exhibit no...
The p21-activated kinase (PAK) homolog, Shk1, is a critical component of multifunctional Ras/Cdc42/PAK complex required for viability, polarized growth and cell shape, sexual differentiation in the fission yeast, Schizosaccharomyces pombe. Substrate targets Shk1 have not previously been described. Here we show that S. pombe polarity factor, Tea1, directly phosphorylated by vitro. We demonstrate further Tea1 cells its level phosphorylation significantly reduced defective function. Consistent...
The p21-activated kinase, Shk1, is required for cell viability, establishment and maintenance of polarity, proper mating response in the fission yeast,Schizosaccharomyces pombe. Previous genetic studies suggested that a presumptive protein methyltransferase, Skb1, functions as positive modulator Shk1. However, unlike Skb1 not viability or S. pombe cells contributes only modestly to regulation morphology under normal growth conditions. Here we demonstrate plays more significant role...
Deregulation of cell polarity proteins has been linked to the processes invasion and metastasis. TRIM62 is a regulator tumour suppressor in breast cancer. Here, we demonstrate that human non-small lung cancer lesions show step-wise loss levels during disease progression, which was associated with poor clinical outcomes. To directly examine role Trim62 development cancer, deleted mutant K-Ras mouse model In this context, haploinsufficiency synergized K-RasG12D mutation promote invasiveness...
The PAK family kinase, Shk1, is an essential regulator of polarized growth in the fission yeast, Schizosaccharomyces pombe. Here we describe characterization a novel member RhoGAP family, Rga8, identified from two-hybrid screen for proteins that interact with Shk1 kinase domain. Although deletion rga8 gene wild type S. pombe cells results no obvious phenotypic defects under normal conditions, it partially suppresses cold-sensitive and morphological carrying hypomorphic allele shk1 gene. By...
Objective To investigate potential functional variants in FTO and SH2B1 genes among Chinese children with obesity. Methods Sanger sequencing of PCR products all exons their flanking regions were performed 338 Han obesity 221 age- sex-matched lean controls. Results A total seven five rare non-synonymous identified SH2B1, respectively. The overall frequencies similar obese (2.37% 0.90% vs. 1.81% 1.36%, P>0.05). However, four out the novel unique to (p>0.05). None was consistently being...
Abstract Background Treatments are often unavailable for rare disease patients, especially in low-and-middle-income countries. Reasons this include lack of financial support therapies and onerous regulatory requirements approval drugs. Other barriers reimbursement, administrative infrastructure, knowledge about diagnosis drug treatment options. The International Rare Diseases Research Consortium set up the Disease Treatment Access Working Group with first objective to develop an essential...
Summary The p21‐activated kinase, Shk1, is required for the proper establishment of cell polarity in fission yeast, Schizosaccharomyces pombe . We showed recently that loss essential Shk1 inhibitor, Skb15, causes significant spindle defects thus implicating as a potential regulator microtubule dynamics. Here, we show cells deficient function have malformed interphase microtubules and mitotic spindles, are hypersensitive to microtubule‐destabilizing drug thiabendazole (TBZ) cold sensitive...
The p21-activated kinase (PAK) homolog Shk1 is essential for cell viability in the fission yeastSchizosaccharomyces pombe. Roles have been established regulation of morphology, sexual differentiation, and mitosis S. In this report, we describe genetic molecular characterization a novel SH3 domain protein, Skb5, identified as result two-hybrid screen interacting proteins. pombe cells carrying deletion skb5 gene exhibit no discernible phenotypic defects under normal growth conditions, but when...
Avicins comprise a class of triterpenoid compounds that exhibit tumor inhibitory activity. Here we show avicin G is to growth the fission yeast Schizosaccharomyces pombe . S. cells treated with lethal concentration (20 μM) exhibited shrunken morphology, indicating adversely affects cell integrity. Cells sublethal (6.5 strong cytokinesis-defective phenotype (multiseptated cells), as well morphology defects. These phenotypes bear resemblance those resulting from loss Rho1 GTPase function in...