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Jiangquan Liao, Benjun Wei, Hengwen Chen, Yongmei Liu, Jie Wang
BACKGROUND: Xuesaitong soft capsule (XST) which consists of panax notoginseng saponin (PNS) has been used to treat ischemic cerebrovascular diseases in China. The therapeutic mechanism of XST has not been elucidated yet from prospective of genomics and bioinformatics. METHODS: A transcriptome analysis was performed to review series concerning middle cerebral artery occlusion (MCAO) rat model and XST intervention after MCAO from Gene Expression Omnibus (GEO) database...
2016: American Journal of Translational Research
Shufeng Li, Qian Qiang, Haitao Shan, Minke Shi, Guangming Gan, Fang Ma, Baojun Chen
AIMS: RB1CC1/FIP200 was essential for autophagosome formation. Therefore, RB1CC1/FIP200 cellular levels are critical for the activation of the autophagy pathways. Following the screen of miRNAs affecting RB1CC1/FIP200 level and rapamycin-induced autophagy, we discovered miR-20a and miR-20b could regulate autophagy by targeting RB1CC1/FIP200. MAIN METHODS: Inhibitory effect of miR-20a and 20b on basal and rapamycin-stimulated autophagy was demonstrated using various autophagic tests including GFP-LC3 puncta analysis, LC3II/LC3I gel shift and TEM observation...
February 15, 2016: Life Sciences
Li-Yi Zhang, Jian-Lin Wu, Hai-Bo Qiu, Sui-Sui Dong, Ying-Hui Zhu, Victor Ho-Fun Lee, Yan-Ru Qin, Yan Li, Juan Chen, Hai-Bo Liu, Jiong Bi, Stephanie Ma, Xin-Yuan Guan, Li Fu
Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy; its mechanisms of development and progression are poorly understood. By high-throughput transcriptome sequencing (RNA-Seq) profiling of three pairs of primary ESCCs and their corresponding non-tumorous tissues, we identified that prostate stem cell antigen (PSCA), a gene that encodes a glycosylphosphatidylinositol-anchored protein, is significantly downregulated in ESCC. Here, we reported decreased expression of PSCA in 188/218 (86.2%) of primary ESCC cases and was negatively regulated by its transcription factor sex-determining region Y-box5 that was significantly associated with the poor differentiation (P = 0...
March 2016: Carcinogenesis
Hana Popelka, Daniel J Klionsky
ULK1 and ATG13 assemble with RB1CC1/FIP200 and ATG101 to form a macroautophagy (hereafter autophagy) induction (ULK1) complex in higher eukaryotes. The yeast counterpart, the Atg1 complex, is comprised of Atg1 and Atg13 (ULK1 and ATG13 homologs), Atg17 (a proposed functional homolog of RB1CC1), and either the Atg101 subunit (in Schizosaccharomyces pombe) or the Atg29-Atg31 heterodimer (in Saccharomyces cerevisiae). With mutual exclusivity of, and no detectable homology between, the Atg29-Atg31 dimer and Atg101, knowledge about the roles of these proteins in autophagy induction is an important piece in the puzzle of understanding the molecular mechanism of autophagy initiation...
September 1, 2015: Autophagy
Nora Hieke, Antje S Löffler, Takeshi Kaizuka, Niklas Berleth, Philip Böhler, Stefan Drießen, Fabian Stuhldreier, Olena Friesen, Kaivon Assani, Katharina Schmitz, Christoph Peter, Britta Diedrich, Jörn Dengjel, Petter Holland, Anne Simonsen, Sebastian Wesselborg, Noboru Mizushima, Björn Stork
Autophagy describes an intracellular process responsible for the lysosome-dependent degradation of cytosolic components. The ULK1/2 complex comprising the kinase ULK1/2 and the accessory proteins ATG13, RB1CC1, and ATG101 has been identified as a central player in the autophagy network, and it represents the main entry point for autophagy-regulating kinases such as MTOR and AMPK. It is generally accepted that the ULK1 complex is constitutively assembled independent of nutrient supply. Here we report the characterization of the ATG13 region required for the binding of ULK1/2...
2015: Autophagy
Chandra B Lebovitz, A Gordon Robertson, Rodrigo Goya, Steven J Jones, Ryan D Morin, Marco A Marra, Sharon M Gorski
Aberrant activation or disruption of autophagy promotes tumorigenesis in various preclinical models of cancer, but whether the autophagy pathway is a target for recurrent molecular alteration in human cancer patient samples is unknown. To address this outstanding question, we surveyed 211 human autophagy-associated genes for tumor-related alterations to DNA sequence and RNA expression levels and examined their association with patient survival outcomes in multiple cancer types with sequence data from The Cancer Genome Atlas consortium...
2015: Autophagy
Stefan Drießen, Niklas Berleth, Olena Friesen, Antje S Löffler, Philip Böhler, Nora Hieke, Fabian Stuhldreier, Christoph Peter, Kay O Schink, Sebastian W Schultz, Harald Stenmark, Petter Holland, Anne Simonsen, Sebastian Wesselborg, Björn Stork
Autophagy represents an intracellular degradation process which is involved in both regular cell homeostasis and disease settings. In recent years, the molecular machinery governing this process has been elucidated. The ULK1 kinase complex consisting of the serine/threonine protein kinase ULK1 and the adapter proteins ATG13, RB1CC1, and ATG101, is centrally involved in the regulation of autophagy initiation. This complex is in turn regulated by the activity of different nutrient- or energy-sensing kinases, including MTOR, AMPK, and AKT...
2015: Autophagy
Jingyu Yao, Lin Jia, Naheed Khan, Chengmao Lin, Sayak K Mitter, Michael E Boulton, Joshua L Dunaief, Daniel J Klionsky, Jun-Lin Guan, Debra A Thompson, David N Zacks
Autophagy regulates cellular homeostasis and response to environmental stress. Within the retinal pigment epithelium (RPE) of the eye, the level of autophagy can change with both age and disease. The purpose of this study is to determine the relationship between reduced autophagy and age-related degeneration of the RPE. The gene encoding RB1CC1/FIP200 (RB1-inducible coiled-coil 1), a protein essential for induction of autophagy, was selectively knocked out in the RPE by crossing Best1-Cre mice with mice in which the Rb1cc1 gene was flanked with Lox-P sites (Rb1cc1(flox/flox))...
2015: Autophagy
Huijun Wei, Jun-Lin Guan
Autophagy is a highly conserved cellular process for degradation of bulk cytoplasmic materials in response to starvation and maintenance of cellular homeostasis. Dysfunction of autophagy is implicated in a variety of diseases including cancer. In a recent study, we devised a system for inducible deletion of an essential autophagy gene Rb1cc1/Fip200 in established tumor cells in vivo and showed that Rb1cc1 is required for maintaining tumor growth. We further investigated the role of the accumulated SQSTM1 in Rb1cc1-null autophagy-deficient tumor cells...
2015: Autophagy
A A Sleptsov, M S Nazarenko, I N Lebedev, N A Skriabin, A V Frolov, V A Popov, L S Barbarash, V P Puzyrev
The first data on the existence of multiple genomic rearrangements, such as copy number variation (CNV) and copy neutral loss of heterozygosity, in vascular tissues and peripheral blood leukocytes from patients with atherosclerosis, are presented. Compared to internal mammary arteries and peripheral blood leukocytes, right coronary arteries in the atherosclerotic plaque area presented with a higher CNV length and number of genes located in their vicinity. In each of the patients, 6-16% of CNVs were common to the three types of tissues examined...
August 2014: Genetika
T F Godoy, G C M Moreira, C Boschiero, A A Gheyas, G Gasparin, M Paduan, S C S Andrade, H Montenegro, D W Burt, M C Ledur, L L Coutinho
Genetic improvement is important for the poultry industry, contributing to increased efficiency of meat production and quality. Because breast muscle is the most valuable part of the chicken carcass, knowledge of polymorphisms influencing this trait can help breeding programs. Therefore, the complete genome of 18 chickens from two different experimental lines (broiler and layer) from EMBRAPA was sequenced, and SNPs and INDELs were detected in a QTL region for breast muscle deposition on chicken chromosome 2 between microsatellite markers MCW0185 and MCW0264 (105,849-112,649 kb)...
April 2015: Animal Genetics
Chieko Kishi-Itakura, Ikuko Koyama-Honda, Eisuke Itakura, Noboru Mizushima
Autophagy is mediated by a unique organelle, the autophagosome. Autophagosome formation involves a number of autophagy-related (ATG) proteins and complicated membrane dynamics. Although the hierarchical relationships of ATG proteins have been investigated, how individual ATG proteins or their complexes contribute to the organization of the autophagic membrane remains largely unknown. Here, systematic ultrastructural analysis of mouse embryonic fibroblasts (MEFs) and HeLa cells deficient in various ATG proteins reveals that the emergence of the isolation membrane (phagophore) requires FIP200 (also known as RB1CC1), ATG9A and phosphatidylinositol (PtdIns) 3-kinase activity...
September 15, 2014: Journal of Cell Science
Q B Luo, X Y Song, C L Ji, X Q Zhang, D X Zhang
The process of heat regulation is complex and its exact molecular mechanism is not fully understood. In this study, to investigate the global gene regulation response to acute heat exposure, gene microarrays were exploited to analyze the effects of heat stress on three tissues (brain, liver, leg muscle) of the yellow broiler chicken (Gallus gallus). We detected 166 differentially expressed genes (DEGs) in the brain, 219 in the leg muscle and 317 in the liver. Six of these genes were differentially expressed in all three tissues and were validated by qRT-PCR, and included heat shock protein genes (HSPH1, HSP25), apoptosis-related genes (RB1CC1, BAG3), a cell proliferation and differentiation-related gene (ID1) and the hunger and energy metabolism related gene (PDK)...
August 10, 2014: Gene
Sebastian Alers, Sebastian Wesselborg, Björn Stork
During the past 20 years, autophagy signaling has entered the main stage of the cell biological theater. Autophagy represents an intracellular degradation process that is involved in both the bulk recycling of cytoplasmic components and the selective removal of organelles, protein aggregates, or intracellular pathogens. The understanding of autophagy has been greatly facilitated by the characterization of the molecular machinery governing this process. In yeast, initiation of autophagy is controlled by the Atg1 kinase complex, which is composed of the Ser/Thr kinase Atg1, the adaptor protein Atg13, and the ternary complex of Atg17-Atg31-Atg29...
June 2014: Autophagy
Mahipal V Suraneni, John R Moore, Dingxiao Zhang, Mark Badeaux, Marc D Macaluso, John DiGiovanni, Donna Kusewitt, Dean G Tang
15-Lipoxygenase-2 (15-LOX2) is a human-specific lipid-peroxidizing enzyme most prominently expressed in epithelial cells of normal human prostate but downregulated or completely lost in>70% of prostate cancer (PCa) cases. Transgenic expression of 15-LOX2 in the mouse prostate surprisingly causes hyperplasia. Here we first provide evidence that 15-LOX2-induced prostatic hyperplasia does not progress to PCa even in p53(+/-) or p53(-/-) background. More important, by generating 15-LOX2; Hi-Myc double transgenic (dTg) mice, we show that 15-LOX2 expression inhibits Myc-induced PCa development, such that in the 3-month- and 6-month-old dTg mice, there is a significant reduction in prostate intraneoplasia (PIN) and PCa prevalent in age-matched Hi-Myc prostates...
2014: Cell Cycle
Xia Li, Xuechao Wan, Hongbing Chen, Shu Yang, Yiyang Liu, Wenjuan Mo, Delong Meng, Wenting Du, Yan Huang, Hai Wu, Jingqiang Wang, Tao Li, Yao Li
OBJECTIVE: We aimed to investigate the contribution of microRNA-133b (miR-133b) in prostate cancer cell proliferation, cell cycle, and apoptosis. We also examined expression of miR-133b in prostate cancer tissues, and evaluated the prognostic significance of miR-133b, as well as its target gene RB1CC1 in patients with prostate cancer after radical prostatectomy. EXPERIMENTAL DESIGN: miR-133b mimics (miR-133bm) and anti-miR-133b were transfected into LNCaP and PC-3 cells...
May 1, 2014: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Péter Nagy, Manuéla Kárpáti, Agnes Varga, Karolina Pircs, Zsolt Venkei, Szabolcs Takáts, Kata Varga, Balázs Erdi, Krisztina Hegedűs, Gábor Juhász
Phagophore-derived autophagosomes deliver cytoplasmic material to lysosomes for degradation and reuse. Autophagy mediated by the incompletely characterized actions of Atg proteins is involved in numerous physiological and pathological settings including stress resistance, immunity, aging, cancer, and neurodegenerative diseases. Here we characterized Atg17/FIP200, the Drosophila ortholog of mammalian RB1CC1/FIP200, a proposed functional equivalent of yeast Atg17. Atg17 disruption inhibits basal, starvation-induced and developmental autophagy, and interferes with the programmed elimination of larval salivary glands and midgut during metamorphosis...
March 2014: Autophagy
Seung-Hyun Ro, Chang Hwa Jung, Wendy S Hahn, Xin Xu, Young-Mi Kim, Young Sung Yun, Ji-Man Park, Kwan Hyun Kim, Minchul Seo, Tae-Youl Ha, Edgar A Arriaga, David A Bernlohr, Do-Hyung Kim
ULK1 (unc-51 like kinase 1) is a serine/threonine protein kinase that plays a key role in regulating the induction of autophagy. Recent studies using autophagy-defective mouse models, such as atg5- or atg7-deficient mice, revealed an important function of autophagy in adipocyte differentiation. Suppression of adipogenesis in autophagy-defective conditions has made it difficult to study the roles of autophagy in metabolism of differentiated adipocytes. In this study, we established autophagy defective-differentiated 3T3-L1 adipocytes, and investigated the roles of Ulk1 and its close homolog Ulk2 in lipid and glucose metabolism using the established adipocytes...
December 2013: Autophagy
Di Ma, Matthew M Molusky, Jianrui Song, Chun-Rui Hu, Fang Fang, Crystal Rui, Anna V Mathew, Subramaniam Pennathur, Fei Liu, Ji-Xin Cheng, Jun-Lin Guan, Jiandie D Lin
Nonalcoholic fatty liver disease is a metabolic disorder commonly associated with obesity. A subset of nonalcoholic fatty liver disease patients further develops nonalcoholic steatohepatitis that is characterized by chronic liver injury, inflammation, and fibrosis. Recent work has implicated the autophagy pathway in the mobilization and oxidation of triglycerides from lipid droplets. However, whether impaired autophagy in hepatocytes drives excess fat accumulation in the liver remains controversial. In addition, the role of autophagy in protecting the liver from gut endotoxin-induced injury has not been elucidated...
October 2013: Molecular Endocrinology
Myungjin Kim, Hae Li Park, Hwan-Woo Park, Seung-Hyun Ro, Samuel G Nam, John M Reed, Jun-Lin Guan, Jun Hee Lee
Autophagy-related 1 (Atg1)/Unc-51-like protein kinases (ULKs) are evolutionarily conserved proteins that play critical physiological roles in controlling autophagy, cell growth and neurodevelopment. RB1-inducible coiled-coil 1 (RB1CC1), also known as PTK2/FAK family-interacting protein of 200 kDa (FIP200) is a recently discovered binding partner of ULK1. Here we isolated the Drosophila RB1CC1/FIP200 homolog (Fip200/CG1347) and showed that it mediates Atg1-induced autophagy as a genetically downstream component in diverse physiological contexts...
August 2013: Autophagy
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