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William E Barry et al.
eLife, 5 (2016-05-18)
Although mutations in HNF4A were identified as the cause of Maturity Onset Diabetes of the Young 1 (MODY1) two decades ago, the mechanisms by which this nuclear receptor regulates glucose homeostasis remain unclear. Here we report that loss of Drosophila...
Shaun D McCullough et al.
Proceedings of the National Academy of Sciences of the United States of America, 109(52), 21319-21324 (2012-12-14)
Spinocerebellar ataxia type 7 (SCA7) is an autosomal-dominant neurodegenerative disorder that results from polyglutamine expansion of the ataxin-7 (ATXN7) protein. Remarkably, although mutant ATXN7 is expressed throughout the body, pathology is restricted primarily to the cerebellum and retina. One major...
Stacia L Koppenhafer et al.
Molecular cancer research : MCR, 18(1), 91-104 (2019-10-28)
Inhibition of ribonucleotide reductase (RNR), the rate-limiting enzyme in the synthesis of deoxyribonucleotides, causes DNA replication stress and activates the ataxia telangiectasia and rad3-related protein (ATR)-checkpoint kinase 1 (CHK1) pathway. Notably, a number of different cancers, including Ewing sarcoma tumors...
Adetutu T Egunsola et al.
The Journal of clinical investigation, 127(4), 1475-1484 (2017-03-07)
Shohat-type spondyloepimetaphyseal dysplasia (SEMD) is a skeletal dysplasia that affects cartilage development. Similar skeletal disorders, such as spondyloepiphyseal dysplasias, are linked to mutations in type II collagen (COL2A1), but the causative gene in SEMD is not known. Here, we have...
Hui-Ran Fan et al.
EBioMedicine, 34, 201-213 (2018-07-31)
An imbalance between neuronal excitation and inhibition represents a core feature in multiple neuropsychiatry disorders, necessitating the development of novel strategies to calibrate the excitatory-inhibitory balance of therapeutics. Here we identify a natural compound quercetin that reduces prefrontal cortical GABAergic...
Alexander V Gopanenko et al.
Nucleic acids research, 45(15), 9121-9137 (2017-07-02)
Ribosomal proteins are involved in many cellular processes through interactions with various RNAs. Here, applying the photoactivatable-ribonucleoside-enhanced cross-linking and immunoprecipitation approach to HEK293 cells overproducing ribosomal protein (rp) eS1, we determined the products of RNU5A-1 and RNU11 genes encoding U5...
Xiaoqian Jing et al.
Cancer research, 79(18), 4650-4664 (2019-06-30)
Nucleotide supply is essential for DNA replication in proliferating cells, including cancer cells. Ribose-phosphate diphosphokinase 1 (PRPS1) is a key enzyme to produce the consensus precursor of nucleotide synthesis. PRPS1 participates in the pentose phosphate pathway (PPP) by catalyzing the...
Hui-Zi Chen et al.
Nature cell biology, 14(11), 1192-1202 (2012-10-16)
The endocycle is a variant cell cycle consisting of successive DNA synthesis and gap phases that yield highly polyploid cells. Although essential for metazoan development, relatively little is known about its control or physiologic role in mammals. Using lineage-specific cre...
Shuliang Chen et al.
Proceedings of the National Academy of Sciences of the United States of America, 115(27), E6237-E6244 (2018-06-20)
The endoplasmic reticulum (ER) forms a contiguous network of tubules and sheets that is predominantly associated with the cell cortex in yeast. Upon treatment with rapamycin, the ER undergoes degradation by selective autophagy. This process, termed ER-phagy, requires Atg40, a...
Xing Lu et al.
Comparative biochemistry and physiology. Toxicology & pharmacology : CBP, 192, 40-49 (2016-12-13)
Mercury is a widespread toxicant in aquatic environment that can cause deleterious effects on fish. Although a number of mercury-regulated genes have been investigated in adult fish, the transcriptional responses of fish larvae to acute mercury exposure are not well...
Dong-E Tang et al.
Cancer science, 110(10), 3145-3156 (2019-08-09)
Yes-associated protein (YAP) is a component of the canonical Hippo signaling pathway that is known to play essential roles in modulating organ size, development, and tumorigenesis. Activation or upregulation of YAP1, which contributes to cancer cell survival and chemoresistance, has...
Shawn Lu Wen Tan et al.
Cell, 169(6), 1105-1118 (2017-06-03)
Mutations truncating a single copy of the tumor suppressor, BRCA2, cause cancer susceptibility. In cells bearing such heterozygous mutations, we find that a cellular metabolite and ubiquitous environmental toxin, formaldehyde, stalls and destabilizes DNA replication forks, engendering structural chromosomal aberrations. Formaldehyde...
Teisha J Rowland et al.
Proceedings of the National Academy of Sciences of the United States of America, 116(37), 18488-18497 (2019-08-28)
Telomerase is pathologically reactivated in most human cancers, where it maintains chromosomal telomeres and allows immortalization. Because telomerase reverse transcriptase (TERT) is usually the limiting component for telomerase activation, numerous studies have measured TERT mRNA levels in populations of cells...
S Zhu et al.
Oncogene, 35(14), 1847-1856 (2015-06-30)
CD44E is a frequently overexpressed variant of CD44 in gastric cancer. Mechanisms that regulate CD44 splicing and expression in gastric cancer remain unknown. Herein, we investigated the role of DARPP-32 (dopamine and cyclic adenosine monophosphate-regulated phosphoprotein, Mr 32000) in promoting...
Xiaoyan Yang et al.
The Journal of clinical investigation, 127(4), 1505-1516 (2017-03-14)
SIRT2 is a cytoplasmic sirtuin that plays a role in various cellular processes, including tumorigenesis, metabolism, and inflammation. Since these processes require iron, we hypothesized that SIRT2 directly regulates cellular iron homeostasis. Here, we have demonstrated that SIRT2 depletion results...
Fatima Kamal et al.
Cell reports, 31(11), 107766-107766 (2020-06-20)
The type VI secretion system (T6SS) is a lethal microbial weapon that injects a large needle-like structure carrying toxic effectors into recipient cells through physical penetration. How recipients respond to physical force and effectors remains elusive. Here, we use a...
WooKee Min et al.
Nature communications, 4, 2993-2993 (2013-12-21)
Damaged replication forks activate poly(ADP-ribose) polymerase 1 (PARP1), which catalyses poly(ADP-ribose) (PAR) formation; however, how PARP1 or poly(ADP-ribosyl)ation is involved in the S-phase checkpoint is unknown. Here we show that PAR, supplied by PARP1, interacts with Chk1 via a novel...
Bhupesh K Prusty et al.
Frontiers in cellular and infection microbiology, 8, 183-183 (2018-06-15)
Obligate intracellular pathogenic Chlamydia trachomatis express several serine proteases whose roles in chlamydial development and pathogenicity are not completely understood. The chlamydial protease CPAF is expressed during the replicative phase of the chlamydial developmental cycle and is secreted into the...
Jinxin Xu et al.
Structure (London, England : 1993), 25(8), 1251-1263 (2017-07-18)
E-Cadherin is a major component of adherens junctions on cell surfaces. SNX16 is a unique member of sorting nexins that contains a coiled-coil (CC) domain downstream of the PX domain. We report here that SNX16 regulates the recycling trafficking of...
Xi Tang et al.
Oncotarget, 5(5), 1352-1362 (2014-03-25)
The development of effective therapies inhibiting prostate cancer progression and metastasis may substantially impact prostate cancer mortality and potentially reduce the rates of invasive treatments by enhancing the safety of active surveillance strategies. Hepsin (HPN) is a cell surface serine...
Yingxiao Shi et al.
Nature medicine, 24(3), 313-325 (2018-02-06)
An intronic GGGGCC repeat expansion in C9ORF72 is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), but the pathogenic mechanism of this repeat remains unclear. Using human induced motor neurons (iMNs), we found that repeat-expanded...
Leanne J M Schmitz et al.
eLife, 6 (2017-12-05)
Glutamatergic synapses rely on AMPA receptors (AMPARs) for fast synaptic transmission and plasticity. AMPAR auxiliary proteins regulate receptor trafficking, and modulate receptor mobility and its biophysical properties. The AMPAR auxiliary protein Shisa7 (CKAMP59) has been shown to interact with AMPARs...
Yunfeng Ju et al.
Endocrinology, 153(11), 5522-5534 (2012-10-02)
5-Aminolevulinic acid synthase 1 (ALAS1) is a rate-limiting enzyme for heme biosynthesis in mammals. Heme is essential for the catalytic activities of P450 enzymes including steroid metabolic enzymes. Nuclear receptor 5A (NR5A) family proteins, steroidogenic factor-1 (SF-1), and liver receptor...
Yunhao Tan et al.
Nature, 475(7357), 506-509 (2011-07-08)
Legionella pneumophila actively modulates host vesicle trafficking pathways to facilitate its intracellular replication with effectors translocated by the Dot/Icm type IV secretion system (T4SS). The SidM/DrrA protein functions by locking the small GTPase Rab1 into an active form by its...
Kathrin Landgraf et al.
Cell reports, 33(3), 108295-108295 (2020-10-22)
TMEM18 is the strongest candidate for childhood obesity identified from GWASs, yet as for most GWAS-derived obesity-susceptibility genes, the functional mechanism remains elusive. We here investigate the relevance of TMEM18 for adipose tissue development and obesity. We demonstrate that adipocyte...
A Conserved NRDE-2/MTR-4 Complex Mediates Nuclear RNAi in Caenorhabditis elegans.
Wan, et al.
Genetics, 216, 1071-1085 (2021)
Yuanlong Ge et al.
Protein & cell, 10(11), 808-824 (2019-05-23)
While the majority of all human cancers counteract telomere shortening by expressing telomerase, ~15% of all cancers maintain telomere length by a telomerase-independent mechanism known as alternative lengthening of telomeres (ALT). Here, we show that high load of intrinsic DNA damage...
Shuji Matsuda et al.
Molecular neurodegeneration, 4, 41-41 (2009-10-24)
Alzheimer disease (AD) is characterized by senile plaques, which are mainly composed of beta amyloid (Abeta) peptides. Abeta is cleaved off from amyloid precursor protein (APP) with consecutive proteolytic processing by beta-secretase and gamma-secretase. Here, we show that CD74, the...
Rocio Acuna-Hidalgo et al.
PLoS genetics, 13(3), e1006683-e1006683 (2017-03-28)
Schinzel-Giedion syndrome (SGS) is a rare developmental disorder characterized by multiple malformations, severe neurological alterations and increased risk of malignancy. SGS is caused by de novo germline mutations clustering to a 12bp hotspot in exon 4 of SETBP1. Mutations in...
Tomohiro Furukawa et al.
Cell chemical biology, 27(11), 1396-1409 (2020-09-06)
Aflatoxin contamination of crops is a serious problem worldwide. Utilization of aflatoxin production inhibitors is attractive, as the elucidation of their modes of action contributes to clarifying the mechanism of aflatoxin production. Here, we identified mitochondrial protease ClpP as the...
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