A5100331356- Receptor Mechanisms and Signaling
- DNA Repair Mechanisms
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- RNA Interference and Gene Delivery
- Cancer-related gene regulation
- Neuropeptides and Animal Physiology
- Lipid Membrane Structure and Behavior
- CRISPR and Genetic Engineering
- MicroRNA in disease regulation
- Genomics and Chromatin Dynamics
- Connexins and lens biology
- Protein Kinase Regulation and GTPase Signaling
- Natural product bioactivities and synthesis
- Plant biochemistry and biosynthesis
- Antimicrobial agents and applications
- Insect symbiosis and bacterial influences
- Bioinformatics and Genomic Networks
- Histone Deacetylase Inhibitors Research
- Animal Genetics and Reproduction
- Enzyme Structure and Function
- Cancer-related Molecular Pathways
- Heme Oxygenase-1 and Carbon Monoxide
- PI3K/AKT/mTOR signaling in cancer
Tsinghua University
2015-2025
Shenyang Medical College
2025
Chengdu Research Base of Giant Panda Breeding
2025
Nanjing Medical University
2025
Jiangsu Province Hospital
2025
Shenzhen University Health Science Center
2021-2024
Affiliated Hospital of Qingdao University
2021-2024
Center for Life Sciences
2011-2024
Shenzhen Second People's Hospital
2022-2024
Tianjin Medical University Cancer Institute and Hospital
2014-2024
The crystal structure of the β2-adrenergic receptor (β2AR) bound to G protein adenylyl cyclase stimulatory (Gs) captured complex in a nucleotide-free state (β2AR-Gsempty). Unfortunately, β2AR-Gsempty does not provide clear explanation for coupling specificity. Evidence from several sources suggests existence transient between β2AR and GDP-bound Gs (β2AR-GsGDP) that may represent an intermediate on way formation contribute Here we present with carboxyl terminal 14 amino acids Gαs along...
R-loops are three-stranded structures that can pose threats to genome stability. RNase H1 precisely recognizes drive their resolution within the genome, but underlying mechanism is unclear. Here, we report ARID1A with high affinity in an ATM-dependent manner. recruits METTL3 and METTL14 R-loop, leading m6A methylation of R-loop RNA. This modification facilitates recruitment driving its promoting DNA end resection at DSBs, thereby ensuring Depletion ARID1A, METTL3, or leads accumulation...
Numerous studies indicate that Sirtuin 1 (SIRT1), a mammalian nicotinamide adenine dinucleotide (NAD + )-dependent histone deacetylase (HDAC), plays crucial role in p53-mediated stress responses by deacetylating p53. Nevertheless, the acetylation levels of p53 are dramatically increased upon DNA damage, and it is not well understood how SIRT1–p53 interaction regulated during responses. Here, we identified Set7/9 as unique regulator SIRT1. SIRT1 interacts with both vitro vivo. In response to...
Ataxia telangiectasia (A-T) mutated (ATM) kinase orchestrates deoxyribonucleic acid (DNA) damage responses by phosphorylating numerous substrates implicated in DNA repair and cell cycle checkpoint activation. A-T patients mouse models that express no ATM protein undergo normal embryonic development but exhibit pleiotropic defects. In this paper, we report mice carrying homozygous kinase-dead mutations Atm (AtmKD/KD) died during early development. AtmKD/− cells exhibited proliferation defects...
Suppressor of variegation 3–9 homolog 1 (SUV39H1), a histone methyltransferase, catalyzes 3 lysine 9 trimethylation and is involved in heterochromatin organization genome stability. However, the mechanism for regulation enzymatic activity SUV39H1 cancer cells not yet well known. In this study, we identified SET domain-containing protein 7 (SET7/9), as unique regulator activity. response to treatment with adriamycin, DNA damage inducer, SET7/9 interacted vivo, GST pull-down assay confirmed...
Abstract Non-homologous end-joining (NHEJ) is the most prominent DNA double strand break (DSB) repair pathway in mammalian cells. PAXX newest NHEJ factor, which shares structural similarity with known factors—XRCC4 and XLF. Here we report that dispensable for physiological otherwise wild-type mice. Yet Paxx −/− mice require XLF Xlf end-ligation. As such, display severe genomic instability neuronal apoptosis, eventually lead to embryonic lethality. Despite their similarities, only cells, but...
Significance Recent structures of GPCRs in complex with G proteins provide important insights into protein activation by family A and B GPCRs; however, questions remain. We don’t fully understand the mechanism coupling specificity or promiscuity some GPCRs. The β 2 AR preferentially couples to s less efficiently i , yet AR-G has been shown play roles cardiac physiology. To better structural basis for preferential over we used NMR spectroscopy supporting MD simulations study conformational...
Faithful inheritance of parental histones is essential to maintain epigenetic information and cellular identity during cell division. Parental are evenly deposited onto the replicating DNA sister chromatids in a process dependent on MCM2 subunit helicase. However, impact aberrant histone partition human disease such as cancer largely unknown. In this study, we construct model impaired by introducing MCM2-2A mutation (defective binding) MCF-7 breast cells. The resulting reprograms...
FKBP12-rapamycin-associated protein (FRAP) or mammalian target of rapamycin (mTOR) and its effector proteins form a critical signaling pathway that regulates eukaryotic cell growth proliferation. Although the components in this have begun to be identified, little is known about their subcellular localization physiological significance localization. By immunofluorescence, we find both endogenous recombinant FRAP/mTOR show predominantly endoplasmic reticulum (ER) Golgi apparatus. Consistent...
Histone deacetylase inhibitor (HDACi) has been shown to demethylate the mammalian genome, which further strengthens concept that DNA methylation and histone modifications interact in regulation of gene expression. Here, we report an HDAC inhibitor, depsipeptide, exhibited significant demethylating activity on promoters several genes, including p16, SALL3, GATA4 human lung cancer cell lines H719 H23, colon line HT-29, pancreatic PANC1. Although expression methyltransferase 1 (DNMT1) was not...
Mammalian target of rapamycin (mTOR) forms two complexes, mTORC1 and mTORC2, that play central roles in cell growth functions. Only is directly inhibited by the immunosuppressive drug rapamycin. Despite recent progress identifying new components functions mTOR pathway, relatively little known about spatial arrangement signaling underlying mechanisms. In a previous study, we showed large proportion localized to endoplasmic reticulum (ER) Golgi many common lines. Here, report identification an...
Classical nonhomologous end joining (C-NHEJ) is a major mammalian DNA double-strand break (DSB) repair pathway that required for assembly of antigen receptor variable region gene segments by V(D)J recombination. Recombination activating endonuclease initiates recombination generating DSBs between two coding and flanking signal sequences (RS), with the ends RS joined C-NHEJ to form joins joins, respectively. During C-NHEJ, factor generates as covalently sealed hairpins blunt 5′-phosphorylated...
Nonhomologous end joining (NHEJ), a major pathway of DNA double-strand break (DSB) repair, is required during lymphocyte development to resolve the programmed DSBs generated Variable, Diverse, and Joining [V(D)J] recombination. XRCC4-like factor (XLF) (also called Cernunnos or NHEJ1) unique component NHEJ pathway. Although germ-line mutations other factors abrogate lead severe combined immunodeficiency (SCID), XLF cause progressive lymphocytopenia that generally less than SCID. Accordingly,...
To obtain the initial crystallization hit and subsequent optimization remain major bottlenecks in membrane protein structure determination. Here we describe an approach to achieve diffraction quality crystals high concentrations of lipid detergent (HILIDE). Initial hits are achieved through a controlled variation protein/lipid/detergent ratios, optimized established by systematic screening with secondary detergents at that adapted for method. The is generally applicable native heterologously...
Significance The development of selective antagonists for muscarinic acetylcholine receptors is challenging due to high homology in orthosteric binding sites among subtypes. Starting from a single amino acid difference the pockets M2 receptor (M2R) and M3R, we developed an M3R-selective antagonist using molecular docking structure-based design. resulting M3R showed up 100-fold selectivity over M2R affinity 1,000-fold vivo. docking-predicted geometry was further confirmed by 3.1 Å crystal...
β-Catenin, which is a key mediator of the wingless-integration site (Wnt)/β-catenin signaling pathway, plays an important role in cell proliferation, fate determination, and tumorigenesis, by regulating expression wide range target genes. Although variety posttranslational modifications are involved β-catenin activity, lysine methylation activity largely unknown. In this study, su(var)3-9, enhancer-of-zeste, trithorax (SET) domain-containing protein 7 (SET7/9), methyltransferase, interacted...