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Figure S1. DMD Module Network. the Network Is Formed by 260 Genes from Disgenet and 1101 Interactions from STRING. Red Nodes Are the Five Seed Candidate Genes
Figure S1. DMD module network. The network is formed by 260 genes from DisGeNET and 1101 interactions from STRING. Red nodes are the five seed candidate genes. Figure S2. DMD module network is more connected than a random module of the same size. It is shown the distribution of the largest connected component of 10.000 random modules of the same size of the DMD module network. The green line (x=260) represents the DMD largest connected component, obtaining a z-score=8.9. Figure S3. Shared genes between BMD and DMD signature. A) A meta-analysis of three microarray datasets (GSE3307, GSE13608 and GSE109178) was performed for the identification of differentially expressed genes (DEGs) in BMD muscle biopsies as compared to normal muscle biopsies. Briefly, the GSE13608 dataset included 6 samples of skeletal muscle biopsy from healthy people and 5 samples from BMD patients. Biopsies were taken from either biceps brachii, triceps brachii or deltoid. The GSE3307 dataset included 17 samples of skeletal muscle biopsy from healthy people and 10 samples from BMD patients. The GSE109178 dataset included 14 samples of controls and 11 samples from BMD patients. For both GSE3307 and GSE10917 datasets, biopsies were taken at the time of diagnosis and from the vastus lateralis. For the meta-analysis of GSE13608, GSE3307 and GSE109178, a random effects model of effect size measure was used to integrate gene expression patterns from the two datasets. Genes with an adjusted p value (FDR) < 0.05 and an │effect size│>2 were identified as DEGs and selected for further analysis. A significant number of DEGs (p<0.001) were in common with the DMD signature genes (blue nodes), as determined by a hypergeometric test assessing the significance of the overlap between the BMD DEGs and the number of DMD signature genes B) MCODE analysis of the overlapping genes between BMD DEGs and DMD signature genes. -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
NUAK2 Amplification Coupled with PTEN Deficiency Promotes Melanoma Development Via CDK Activation
Published OnlineFirst April 1, 2015; DOI: 10.1158/0008-5472.CAN-13-3209 Cancer Therapeutics, Targets, and Chemical Biology Research NUAK2 Amplification Coupled with PTEN Deficiency Promotes Melanoma Development via CDK Activation Takeshi Namiki1,2,3, Tomonori Yaguchi2, Kenta Nakamura2,4, Julio C. Valencia1, Sergio G. Coelho1, Lanlan Yin1, Masakazu Kawaguchi1, Wilfred D. Vieira1, Yasuhiko Kaneko5, Atsushi Tanemura6, Ichiro Katayama6, Hiroo Yokozeki3, Yutaka Kawakami2, and Vincent J. Hearing1 Abstract The AMPK-related kinase NUAK2 has been implicated in number of cells in S phase. NUAK2 silencing and inactivation of melanoma growth and survival outcomes, but its therapeutic the PI3K pathway efficiently controlled CDK2 expression, where- utility has yet to be confirmed. In this study, we show how as CDK2 inactivation specifically abrogated the growth of its genetic amplification in PTEN-deficient melanomas may NUAK2-amplified and PTEN-deficient melanoma cells. Immu- rationalize the use of CDK2 inhibitors as a therapeutic strategy. nohistochemical analyses confirmed an association of CDK2 Analysis of array-CGH data revealed that PTEN deficiency is expression with NUAK2 amplification and p-Akt expression in coupled tightly with genomic amplification encompassing the melanomas. Finally, pharmacologic inhibition of CDK2 was NUAK2 locus, a finding strengthened by immunohistochemical sufficient to suppress the growth of NUAK2-amplified and evidence that phospho-Akt overexpression was correlated with PTEN-deficient melanoma cells in vitro and in vivo. Overall, our NUAK2 expression in clinical specimens of acral melanoma. results show how CDK2 blockade may offer a promising therapy Functional studies in melanoma cells showed that inactivation for genetically defined melanomas, where NUAK2 is amplified of the PI3K pathway upregulated p21 expression and reduced the and PTEN is deleted. -
Toxicogenomic Approach to Impact Assessment of Whole Wastewater Effluents and Development of Effluent- Title Responsive Biomarker
Toxicogenomic Approach to Impact Assessment of Whole Wastewater Effluents and Development of Effluent- Title Responsive Biomarker Author(s) 山村, 宏江 Citation 北海道大学. 博士(工学) 甲第11137号 Issue Date 2013-09-25 DOI 10.14943/doctoral.k11137 Doc URL http://hdl.handle.net/2115/77180 Type theses (doctoral) File Information Hiroe_Yamamura.pdf Instructions for use Hokkaido University Collection of Scholarly and Academic Papers : HUSCAP Doctoral Thesis Toxicogenomic Approach to Impact Assessment of Whole Wastewater Effluents and Development of Effluent-Responsive Biomarker Hiroe Hara-Yamamura Acknowledgement My doctoral research works presented here cannot be completed without a numerous number of tangible and intangible supports from my peers, my supervisor, instructors, friends, and family. I would first express my deepest gratitude to Prof. Satoshi OKABE for his technical advices and crisp ideas which often came to break the deadlock of my research progress, and for continued provision of another chance to me, even in the least fruitful season. Indeed, my three years in Prof. OKABE’s lab was “luxuri- ous” time in my life with a lot of supports, encouragements, and chances. In addition, I appreciate both Prof. Daisuke SANO and Dr. Satoshi ISHII for offering their insights on my experimental design and data analysis as well as giving me words of encouragements from time to time. Also, thank you to Prof. Takashi KUSUI from Toyama Prefectural University for his assistance to bioassay techniques and valuable discussion dur- ing my 1st year and 2nd year evaluation presentations. Furthermore, I would like to express my gratitude to specific efforts kindly provide by: Mr. Kenzo Kudo, Prof. -
GSTP1 Is a Driver of Triple-Negative Breast Cancer Cell Metabolism and Pathogenicity
Article GSTP1 Is a Driver of Triple-Negative Breast Cancer Cell Metabolism and Pathogenicity Graphical Abstract Authors Sharon M. Louie, Elizabeth A. Grossman, Lisa A. Crawford, ..., Andrei Goga, Eranthie Weerapana, Daniel K. Nomura Correspondence [email protected] In Brief Using a reactivity-based chemoproteomic platform, Louie et al. have identified GSTP1 as a triple-negative breast cancer target that, when inhibited, impairs breast cancer pathogenicity through inhibiting GAPDH activity and downstream metabolism and signaling pathways. Highlights d We used chemoproteomics to profile metabolic drivers of breast cancer d GSTP1 is a novel triple-negative breast cancer-specific target d GSTP1 inhibition impairs triple-negative breast cancer pathogenicity d GSTP1 inhibition impairs GAPDH activity to affect metabolism and signaling Louie et al., 2016, Cell Chemical Biology 23, 1–12 May 19, 2016 ª 2016 Elsevier Ltd. http://dx.doi.org/10.1016/j.chembiol.2016.03.017 Please cite this article in press as: Louie et al., GSTP1 Is a Driver of Triple-Negative Breast Cancer Cell Metabolism and Pathogenicity, Cell Chemical Biology (2016), http://dx.doi.org/10.1016/j.chembiol.2016.03.017 Cell Chemical Biology Article GSTP1 Is a Driver of Triple-Negative Breast Cancer Cell Metabolism and Pathogenicity Sharon M. Louie,1 Elizabeth A. Grossman,1 Lisa A. Crawford,2 Lucky Ding,1 Roman Camarda,3 Tucker R. Huffman,1 David K. Miyamoto,1 Andrei Goga,3 Eranthie Weerapana,2 and Daniel K. Nomura1,* 1Departments of Chemistry and Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA 2Department of Chemistry, Boston College, Chestnut Hill, MA 02467, USA 3Department of Cell and Tissue Biology and Medicine, University of California, San Francisco, San Francisco, CA 94143, USA *Correspondence: [email protected] http://dx.doi.org/10.1016/j.chembiol.2016.03.017 SUMMARY subtypes that are correlated with heightened malignancy and poor prognosis remain poorly understood. -
NUAK2 Amplification Coupled with PTEN Deficiency Promotes Melanoma Development Via CDK Activation
Published OnlineFirst April 1, 2015; DOI: 10.1158/0008-5472.CAN-13-3209 Cancer Therapeutics, Targets, and Chemical Biology Research NUAK2 Amplification Coupled with PTEN Deficiency Promotes Melanoma Development via CDK Activation Takeshi Namiki1,2,3, Tomonori Yaguchi2, Kenta Nakamura2,4, Julio C. Valencia1, Sergio G. Coelho1, Lanlan Yin1, Masakazu Kawaguchi1, Wilfred D. Vieira1, Yasuhiko Kaneko5, Atsushi Tanemura6, Ichiro Katayama6, Hiroo Yokozeki3, Yutaka Kawakami2, and Vincent J. Hearing1 Abstract The AMPK-related kinase NUAK2 has been implicated in number of cells in S phase. NUAK2 silencing and inactivation of melanoma growth and survival outcomes, but its therapeutic the PI3K pathway efficiently controlled CDK2 expression, where- utility has yet to be confirmed. In this study, we show how as CDK2 inactivation specifically abrogated the growth of its genetic amplification in PTEN-deficient melanomas may NUAK2-amplified and PTEN-deficient melanoma cells. Immu- rationalize the use of CDK2 inhibitors as a therapeutic strategy. nohistochemical analyses confirmed an association of CDK2 Analysis of array-CGH data revealed that PTEN deficiency is expression with NUAK2 amplification and p-Akt expression in coupled tightly with genomic amplification encompassing the melanomas. Finally, pharmacologic inhibition of CDK2 was NUAK2 locus, a finding strengthened by immunohistochemical sufficient to suppress the growth of NUAK2-amplified and evidence that phospho-Akt overexpression was correlated with PTEN-deficient melanoma cells in vitro and in vivo. Overall, our NUAK2 expression in clinical specimens of acral melanoma. results show how CDK2 blockade may offer a promising therapy Functional studies in melanoma cells showed that inactivation for genetically defined melanomas, where NUAK2 is amplified of the PI3K pathway upregulated p21 expression and reduced the and PTEN is deleted. -
Human Kinases Info Page
Human Kinase Open Reading Frame Collecon Description: The Center for Cancer Systems Biology (Dana Farber Cancer Institute)- Broad Institute of Harvard and MIT Human Kinase ORF collection from Addgene consists of 559 distinct human kinases and kinase-related protein ORFs in pDONR-223 Gateway® Entry vectors. All clones are clonal isolates and have been end-read sequenced to confirm identity. Kinase ORFs were assembled from a number of sources; 56% were isolated as single cloned isolates from the ORFeome 5.1 collection (horfdb.dfci.harvard.edu); 31% were cloned from normal human tissue RNA (Ambion) by reverse transcription and subsequent PCR amplification adding Gateway® sequences; 11% were cloned into Entry vectors from templates provided by the Harvard Institute of Proteomics (HIP); 2% additional kinases were cloned into Entry vectors from templates obtained from collaborating laboratories. All ORFs are open (stop codons removed) except for 5 (MST1R, PTK7, JAK3, AXL, TIE1) which are closed (have stop codons). Detailed information can be found at: www.addgene.org/human_kinases Handling and Storage: Store glycerol stocks at -80oC and minimize freeze-thaw cycles. To access a plasmid, keep the plate on dry ice to prevent thawing. Using a sterile pipette tip, puncture the seal above an individual well and spread a portion of the glycerol stock onto an agar plate. To patch the hole, use sterile tape or a portion of a fresh aluminum seal. Note: These plasmid constructs are being distributed to non-profit institutions for the purpose of basic -
Supplemental File
SUPPLEMENTARY MATERIALS AND METHODS ### reorder as minimun to maximum relative induction. allks2=cbind(allks,apply(allks,1,sum)) For the different analyses, the macros are as following: allks3=allks2[order(allks2[,length(colnames(allks2))]),] allks5=allks3[,-length(colnames(allks2))] -Heatmap and correlation analyses # check allks5 source("http://bioconductor.org/biocLite.R") biocLite() -Heatmap install.packages("gplots") library("gplots") #Set a color scale "zero centered" #Set Graph title (do one by one) breaks=c(seq(-(max(allks5)), max(allks5) , by = 0.05)) titre = "allkinases SASP " mycol <- colorpanel(n=length(breaks)- titre = "allkinases SASP + p16" 1,low="green",mid="black",high="red") titre = "allkinases SASP + p16 + NFkB" #Load Normalized RT-QPCR table (do one by one) # Heatmap, "symkey = T" allks<-read.table("allkS.txt", header = TRUE, sep = "\t", dec = ",", fill = TRUE, , row.names=1 ) dev.off() allks<-read.table("allkSp16.txt", header = TRUE, sep = heatmap.2(allks5, scale = "none", col = mycol, "\t", dec = ",", fill = TRUE, , row.names=1 ) breaks=breaks, symkey = F, allks<-read.table("allkSp16NFkB.txt", header = TRUE, trace = 'none', cexRow=0.8, cexCol = 1.6, srtCol sep = "\t", dec = ",", fill = TRUE, , row.names=1 ) = 0, keysize = 1.3, -Log2 relative fold changes induction calculation key.title = "", margins = c(8, 10), # matrix of minimun values main = paste("relative FC"," ", titre), min=apply(allks, 2, min ) Rowv=F mat<-matrix(min, length(row.names(allks)),length(colnames(allks)), -corrgram byrow=TRUE) # check mat install.packages("corrgram") -
An Emerging Acral Melanoma Oncogene
www.impactjournals.com/oncotarget/ Oncotarget, Advance Publications 2011 NUAK2: an emerging acral melanoma oncogene Takeshi Namiki1,2, Sergio G. Coelho1, Vincent J. Hearing1 1 Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA 2 Department of Dermatology, Yokohama Minato Red Cross Hospital, Yokohama, Kanagawa 231-0801, Japan Correspondence to: Dr. Takeshi Namiki, email: [email protected] Keywords: NUAK2, acral melanoma, migration, metastasis, oncogene Received: September 9, 2011, Accepted: September 10, 2011, Published: September 10, 2011 Copyright: © Namiki et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT: Recent technological advances in cancer genomics make it possible to dissect complicated genomic aberrations of melanomas. In particular, several specific genomic aberrations including 11q13 amplification and KIT aberrations have been identified in acral melanomas. We recently identified NUAK2 at 1q32 as a promising oncogene in acral melanomas and reported its significant roles in tumorigenesis in melanoma cells using both in vitro and in vivo analyses. NUAK2 as a member of the AMPK family has several intriguing aspects both as an oncogene and as a tumor suppressor gene. Here we review genomic aberrations of melanomas focusing on acral melanomas to emphasize the possible roles -
Inhibition of ERK 1/2 Kinases Prevents Tendon Matrix Breakdown Ulrich Blache1,2,3, Stefania L
www.nature.com/scientificreports OPEN Inhibition of ERK 1/2 kinases prevents tendon matrix breakdown Ulrich Blache1,2,3, Stefania L. Wunderli1,2,3, Amro A. Hussien1,2, Tino Stauber1,2, Gabriel Flückiger1,2, Maja Bollhalder1,2, Barbara Niederöst1,2, Sandro F. Fucentese1 & Jess G. Snedeker1,2* Tendon extracellular matrix (ECM) mechanical unloading results in tissue degradation and breakdown, with niche-dependent cellular stress directing proteolytic degradation of tendon. Here, we show that the extracellular-signal regulated kinase (ERK) pathway is central in tendon degradation of load-deprived tissue explants. We show that ERK 1/2 are highly phosphorylated in mechanically unloaded tendon fascicles in a vascular niche-dependent manner. Pharmacological inhibition of ERK 1/2 abolishes the induction of ECM catabolic gene expression (MMPs) and fully prevents loss of mechanical properties. Moreover, ERK 1/2 inhibition in unloaded tendon fascicles suppresses features of pathological tissue remodeling such as collagen type 3 matrix switch and the induction of the pro-fbrotic cytokine interleukin 11. This work demonstrates ERK signaling as a central checkpoint to trigger tendon matrix degradation and remodeling using load-deprived tissue explants. Tendon is a musculoskeletal tissue that transmits muscle force to bone. To accomplish its biomechanical function, tendon tissues adopt a specialized extracellular matrix (ECM) structure1. Te load-bearing tendon compart- ment consists of highly aligned collagen-rich fascicles that are interspersed with tendon stromal cells. Tendon is a mechanosensitive tissue whereby physiological mechanical loading is vital for maintaining tendon archi- tecture and homeostasis2. Mechanical unloading of the tissue, for instance following tendon rupture or more localized micro trauma, leads to proteolytic breakdown of the tissue with severe deterioration of both structural and mechanical properties3–5. -
Analysis of the Role of FRMD5 in the Biology of Papillary Thyroid Carcinoma
International Journal of Molecular Sciences Article Analysis of the Role of FRMD5 in the Biology of Papillary Thyroid Carcinoma Agata M. Gaweł 1,2, Maciej Ratajczak 3, Ewa Gajda 4 , Małgorzata Grzanka 1 , Agnieszka Paziewska 5,6, Marta Cie´slicka 7, Maria Kulecka 5, Małgorzata Oczko-Wojciechowska 7 and Marlena Godlewska 1,* 1 Centre of Postgraduate Medical Education, Department of Biochemistry and Molecular Biology, Marymoncka 99/103, 01-813 Warsaw, Poland; [email protected] (A.M.G.); [email protected] (M.G.) 2 Faculty of Medicine, Medical University of Warsaw, Histology and Embryology Students’ Science Association HESA, Chałubinskiego 5, 02-004 Warsaw, Poland 3 Centre of Postgraduate Medical Education, Department of Endocrinology, Marymoncka 99/103, 01-813 Warsaw, Poland; [email protected] 4 Centre of Postgraduate Medical Education, Department of Immunohematology, Marymoncka 99/103, 01-813 Warsaw, Poland; [email protected] 5 Centre of Postgraduate Medical Education, Department of Gastroenterology, Hepatology and Clinical Oncology, Marymoncka 99/103, 01-813 Warsaw, Poland; [email protected] (A.P.); [email protected] (M.K.) 6 Centre of Postgraduate Medical Education, Department of Neuroendocrinology, Marymoncka 99/103, 01-813 Warsaw, Poland 7 Department of Genetic and Molecular Diagnostics of Cancer, M. Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Wybrzeze Armii Krajowej 15, 44-102 Gliwice, Poland; [email protected] (M.C.); [email protected] (M.O.-W.) * Correspondence: [email protected] Citation: Gaweł, A.M.; Ratajczak, M.; Gajda, E.; Grzanka, M.; Paziewska, A.; Abstract: Background: Thyroid carcinoma (TC) is the most common endocrine system malignancy, Cie´slicka,M.; Kulecka, M.; and papillary thyroid carcinoma (PTC) accounts for >80% of all TC cases. -
PRODUCTS and SERVICES Target List
PRODUCTS AND SERVICES Target list Kinase Products P.1-11 Kinase Products Biochemical Assays P.12 "QuickScout Screening Assist™ Kits" Kinase Protein Assay Kits P.13 "QuickScout Custom Profiling & Panel Profiling Series" Targets P.14 "QuickScout Custom Profiling Series" Preincubation Targets Cell-Based Assays P.15 NanoBRET™ TE Intracellular Kinase Cell-Based Assay Service Targets P.16 Tyrosine Kinase Ba/F3 Cell-Based Assay Service Targets P.17 Kinase HEK293 Cell-Based Assay Service ~ClariCELL™ ~ Targets P.18 Detection of Protein-Protein Interactions ~ProbeX™~ Stable Cell Lines Crystallization Services P.19 FastLane™ Structures ~Premium~ P.20-21 FastLane™ Structures ~Standard~ Kinase Products For details of products, please see "PRODUCTS AND SERVICES" on page 1~3. Tyrosine Kinases Note: Please contact us for availability or further information. Information may be changed without notice. Expression Protein Kinase Tag Carna Product Name Catalog No. Construct Sequence Accession Number Tag Location System HIS ABL(ABL1) 08-001 Full-length 2-1130 NP_005148.2 N-terminal His Insect (sf21) ABL(ABL1) BTN BTN-ABL(ABL1) 08-401-20N Full-length 2-1130 NP_005148.2 N-terminal DYKDDDDK Insect (sf21) ABL(ABL1) [E255K] HIS ABL(ABL1)[E255K] 08-094 Full-length 2-1130 NP_005148.2 N-terminal His Insect (sf21) HIS ABL(ABL1)[T315I] 08-093 Full-length 2-1130 NP_005148.2 N-terminal His Insect (sf21) ABL(ABL1) [T315I] BTN BTN-ABL(ABL1)[T315I] 08-493-20N Full-length 2-1130 NP_005148.2 N-terminal DYKDDDDK Insect (sf21) ACK(TNK2) GST ACK(TNK2) 08-196 Catalytic domain