DOCSLIB.ORG

Supplementary Table 2

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Table S2. Cell Pathways Affected by Epigenetic Therapy Cell Cycle Core DNA Damage Response 5-AZA 5-AZA+MS-275 5-AZA 5-AZA+MS-275 P-value: 8.3 x 10-8 P-value: 1.5 x 10-14 P-value: 3.0 x 10-8 P-value: 7.8 x 10-8 BUBR1 Aurora-A 14-3-3 sigma 14-3-3 theta CAP-G CAP-G AKT(PKB) AKT(PKB) CDC25A CDC18L (CDC6) ANT ANT CDC7 CDC20 BLM Bax CDK6 CDC45L BMF Bid Cdt1 CDK1 (p34) Bard1 Bik Cyclin B CKS2 Bcl-XL Brca1 Cyclin B2 Cdt1 Bid CDK1 (p34) Cyclin D Cyclin B CDC25A Chk1 Cyclin D3 Cyclin B1 Caspase-4 Cyclin B HP1 alpha Cyclin B2 Cyclin B Cyclin B1 INCENP Cyclin D Cyclin D Cyclin D Kid Cyclin D1 FasR(CD95) Cyclin D1 MAD2a Cyclin D3 G-protein beta/gamma DNA polymerase mu MCM2 E2F2 HMG2 FANCD2 MCM3 Kid HSP70 HMG2 MCM6 Kinase MYT1 Histone H1 HSP70 MCM7 MAD2a Lamin B Histone H1 RPA1 MCM2 Lamin B1 Histone H2AX Rod MCM4 MEK1(MAP2K1) Histone H2B Securin MCM4/6/7 complex MKP-1 Kinase MYT1 Zwilch MCM5 MSH2 NTH1 p14ARF MCM6 NOXA PP2A catalytic p15 MCM7 PKA-cat (cAMP- Survivin dependent) p16INK4 PLK1 PLK3 (CNK) USP1 p19 Securin POLD reg (p12) VEGF-A p21 Survivin PP2A catalytic c-Fos p57 TOP2 RPA1 p21 p18 Rad51 tBid 1 Cell Cycle Core DNA Damage Response 5-AZA 5-AZA+MS-275 5-AZA 5-AZA+MS-275 P-value: 8.3 x 10-8 P-value: 1.5 x 10-14 P-value: 3.0 x 10-8 P-value: 7.8 x 10-8 p21 RanBP2 SAE2 USP1 c-IAP2 p14ARF p21 tBid 2 Apoptosis Tissue Remodeling and Wound Repair 5-AZA 5-AZA+MS-275 5-AZA 5-AZA+MS-275 P-value: 2.9 x 10-6 P-value: 1.5 x 10-7 P-value: 1.2 x 10-10 P-value: 6.8 x 10-5 14-3-3 sigma 14-3-3 theta AKT(PKB) AF-6 AKT(PKB) AGAL Alpha-catenin AKT(PKB) ANT AKT(PKB) C1 inhibitor Adenylate cyclase type III APRIL(TNFSF13) ANT CLF-1 CEACAM5 ARG2 APRIL(TNFSF13) COX-2 (PTGS2) Cyclin D1 ActRIIA Adenylate cyclase CRTL1 DEP-1 Activin A Bax Collagen II E-cadherin BLM Bid Collagen IV Fibrinogen (fibrin) BMF Bik Connexin 45 G-protein alpha-i family Bard1 Brca1 ER81 Galectin-3 Bcl-XL CD70(TNFSF7) FasR(CD95) Galpha(q)-specific frizzled GPCRs Bid CDK1 (p34) Fibulin-1 IBP4 CD70(TNFSF7) Chk1 Fyn ITGB7 COX-2 (PTGS2) Cyclin B1 Galectin-4 Kallikrein 1 Caspase-4 Cyclin D3 Galpha(q)-specific MMP-1 frizzled GPCRs Cyclin D3 DCOR IGF-2 MMP-15 DR3(TNFRSF12) DR3(TNFRSF12) IP3 receptor MMP-9 FN14(TNFRSF12A) FANCD2 ITGB1 MyHC FasR(CD95) G-protein alpha-i Importin PDGF receptor family (karyopherin)-beta Fyn G3P2 LAMA4 PDGF-R-alpha G-protein beta/gamma GRP78 LEKTI PKC HMG2 HMG2 MEK1(MAP2K1) PKC-gamma HSP70 HSP70 MEK1/2 PLAUR (uPAR) Histone H1 Histone H1 MEK3(MAP2K3) Tenascin-C IP3 receptor Histone H2AX MKP-1 Tiam1 JAK3 Histone H2B MMP-14 VEGF-A LPP2 JAK3 MMP-9 Vitronectin 3 Apoptosis Tissue Remodeling and Wound Repair 5-AZA 5-AZA+MS-275 5-AZA 5-AZA+MS-275 P-value: 2.9 x 10-6 P-value: 1.5 x 10-7 P-value: 1.2 x 10-10 P-value: 6.8 x 10-5 LTB LIGHT(TNFSF14) Osteonectin ZO-2 Lamin B LTB PKA-cat (cAMP- c-Fos dependent) Lamin B1 Lyn PKA-cat alpha c-Src MEK1(MAP2K1) PKC-gamma PLAT (TPA) p120-catenin MEK3(MAP2K3) PP2A catalytic PLAU (UPA) p21 MKP-1 PSD-95 PLC-beta p38 MAPK NOXA SPHK1 Protein kinase G1 PKA-cat (cAMP- SSAT RAP-1A dependent) PP2A catalytic Survivin Ski PSD-95 TRAF5 Sno-N Protein kinase G1 UGCG TFPI-2 alpha Protein kinase G1 beta VEGF-A TGF-beta receptor type I RAP-1A c-Fos TIMP3 RanBP2 c-Src Tcf(Lef) SAE2 jBid Tenascin-C Sequestosome 1(p62) nAChR alpha Tenascin-R Syk nAChR alpha-7 Tiam1 TL1A(TNFSF15) p21 Tubulin (in microtubules) Tubulin alpha p38 MAPK Tubulin alpha c-IAP2 tBid Tubulin beta c-Src Versican jBid Vitronectin nAChR alpha ZO-2 p14ARF ZO-3 p21 c-Src tBid eIF4H p15 p21 4 Mitogenic Signaling Protein Synthesis 5-AZA 5-AZA+MS-275 5-AZA 5-AZA+MS-275 P-value: 1.1 x 10-2 P-value: 9.7 x 10-5 P-value: 1.6 x 10-2 P-value: 1.1 x 10-3 14-3-3 epsilon AGAL AKT(PKB) AKT(PKB) AKT(PKB) AKT(PKB) DNMT1 Adenylate cyclase Bcl-XL Adenylate cyclase DNMT3A Aurora-A C/EBPbeta Adenylate cyclase type DNMT3B CDC20 III CALDAG-GEFI Aurora-A G-protein beta/gamma CDK1 (p34) CCL2 Bax Galpha(q)-specific Cyclin B1 frizzled GPCRs CLF-1 Brca1 IP3 receptor G-protein alpha-i family COX-2 (PTGS2) CDC20 JAK3 Galpha(q)-specific frizzled GPCRs Cyclin D CDK1 (p34) MEK1(MAP2K1) JAK3 FasR(CD95) Cyclin B1 MEK3(MAP2K3) Kinase MYT1 G-protein beta/gamma Cyclin D PKA-cat (cAMP- MAT2A dependent) IBP Cyclin D1 PKA-cat alpha PLD1 IGF-2 E-cadherin PLC-beta1 PLK1 IP3 receptor G-protein alpha-i PP2A catalytic PP2A catalytic family LPP2 IBP Selenoprotein P SelM MEF2C Kinase MYT1 TGF-beta receptor Selenoprotein P type I MEK1(MAP2K1) MMP-9 TXNRD1 TXNRD1 MEK1/2 PDGF receptor Tiam1 Tiam1 MEK3(MAP2K3) PDGF-R-alpha c-Src c-Src MKP-1 PKC eIF3S8 p38 MAPK MMP-9 PKC-gamma eIF4H PKA-cat (cAMP- PLK1 dependent) PKA-cat alpha SPHK1 PLAU (UPA) Syndecan-4 5 Mitogenic Signaling Protein Synthesis 5-AZA 5-AZA+MS-275 5-AZA 5-AZA+MS-275 P-value: 1.1 x 10-2 P-value: 9.7 x 10-5 P-value: 1.6 x 10-2 P-value: 1.1 x 10-3 PLC-beta Tiam1 PLGF UGCG RAP-1A VEGF-A RET VEGF-C Sequestosome 1(p62) Vitronectin Tcf(Lef) c-Fos Tiam1 c-Src VEGF-C p21 Vitronectin p38 MAPK c-Src p38beta (MAPK11) p21 6 Oxidative Stress Reduction Calcium Signaling 5-AZA 5-AZA+MS-275 5-AZA 5-AZA+MS-275 P-value: 1.6 x 10-1 P-value: 1.2 x 10-3 P-value: 2.7 x 10-5 P-value: 2.2 x 10-5 14-3-3 sigma AKT(PKB) AKT(PKB) AKT(PKB) ACAA1 Angiotensin II CDO1 Adenylate cyclase AKT(PKB) Bax COX-2 (PTGS2) Adenylate cyclase type III COX-2 (PTGS2) FTL FasR(CD95) Angiotensin II CYP2B6 G-protein alpha-i G-protein beta/gamma Cyclin D1 family FTL G3P2 IGF-2 G-protein alpha-i family G-protein beta/gamma GCL reg IL4RA IL4RA G6PD GSTA1 IP3 receptor JAK3 GCL reg GSTA2 JAK3 LIPS GGT1 GSTA5 LDHA Lyn GSTO2 GSTM2 LIPS PDGF receptor GSTP1 GSTO2 MEF2 PKC HSP70 HSP70 MEF2C PKC-gamma IP3 receptor Heme oxygenase 1 MEK1(MAP2K1) PP2A catalytic JAK3 JAK3 NUR77 PSD-95 LPP2 MAAI PDE3B c-Fos MAAI MGST PKA-cat (cAMP- c-Src dependent) MEK1(MAP2K1) Myoglobin PKA-cat alpha cPKC (conventional) MEK3(MAP2K3) PAM PLC-beta p21 NOX1 PEMT PLC-beta1 p38 MAPK PAM PLA2 PP2A catalytic p38beta (MAPK11) PLC-beta PLCD PSD-95 PLCD PLD1 Protein kinase G1 alpha PSD-95 PSD-95 Protein kinase G1 beta Protein kinase G1 Ribonucleotide RAP-1A alpha reductase Protein kinase G1 beta SCPX RAP-2A 7 Oxidative Stress Reduction Calcium Signaling 5-AZA 5-AZA+MS-275 5-AZA 5-AZA+MS-275 P-value: 1.6 x 10-1 P-value: 1.2 x 10-3 P-value: 2.7 x 10-5 P-value: 2.2 x 10-5 Selenoprotein P SelM Sequestosome 1(p62) Stathmin Selenoprotein P Syk TXNRD1 TXNRD1 WASF1(WAVE1) c-Src c-Fos c-Src c-Src p21 p38 MAPK 8 Immune System Response Inflammatory Response 5-AZA 5-AZA+MS-275 5-AZA 5-AZA+MS-275 P-value: 2.5 x 10-2 P-value: 2.6 x 10-3 P-value: 4.6 x 10-3 P-value: 5.7 x 10-3 AKT(PKB) ADAM17 AKT(PKB) ADAM17 AML1 (RUNX1) AKT(PKB) Bcl-XL AKT(PKB) AP-1 beta subunit Adenylate cyclase Bid Adenylate cyclase Bcl-6 Brca1 C/EBPbeta Bax Bcl-XL CD14 CARD9 Bid C/EBPbeta Cyclin D1 CCL2 CD14 C1 inhibitor Cyclin D3 COX-2 (PTGS2) Eotaxin-3 CALDAG-GEFI Eotaxin-3 Collagen IV G-protein alpha-i family CCL2 Factor B ELAVL1 (HuR) HSP70 CD74 Factor Ba Fyn Hck COX-2 (PTGS2) Factor Bb G-protein beta/gamma Heme oxygenase 1 CXCR4 Factor H HSP70 JAK3 Clusterin G-protein alpha-i Hck LIPS family Cyclin D3 Gelsolin IP3 receptor MMP-1 DAF HLA-C JAK3 MyHC FasR(CD95) HSD17B2 LAMA4 PIP5KI Fyn Hck LIPS PLA2 G-protein beta/gamma Heme oxygenase 1 MEF2 PLA2G10 GADD45 gamma ICAM2 MEF2C PLAUR (uPAR) Gelsolin ICAM3 MEK1(MAP2K1) PLD1 HLA-DM IL4RA MEK3(MAP2K3) PSD-95 HSD17B2 JAK3 PKA-cat (cAMP- Tiam1 dependent) Hck KLRC3 PLAT (TPA) VEGF-A IL4RA LRG PLAU (UPA) Vitronectin IP-30 Lyn PLC-beta1 c-Fos IP3 receptor MCM5 PRDX2 c-Src ITGB1 MHC class I PSD-95 jBid JAK3 MMP-1 Protein kinase G1 beta p38 MAPK 9 Immune System Response Inflammatory Response 5-AZA 5-AZA+MS-275 5-AZA 5-AZA+MS-275 P-value: 2.5 x 10-2 P-value: 2.6 x 10-3 P-value: 4.6 x 10-3 P-value: 5.7 x 10-3 KLRC3 MMP-9 RAP-1A p38beta (MAPK11) Lysozyme MyHC Syk tBid MEK1(MAP2K1) NGAL TGF-beta receptor type I MEK1/2 PDIA3 TLR4 MEK3(MAP2K3) PIP5K1A Tcf(Lef) MHC class I PIP5KI Tiam1 MICB PKC Vitronectin MMP-9 PLD1 c-IAP2 MaxiK alpha subunit PP2A catalytic c-Src NKG2C SERPINA3 (ACT) jBid PDIA3 TRAF5 tBid PKA-cat (cAMP- Tiam1 dependent) PKA-cat alpha VEGF-A PLC-beta c-Fos PLC-beta1 c-Src PP2A catalytic p21 PSMB5 p38 MAPK PSMB8(LMP7) p38beta (MAPK11) RAP-1A Syk TGF-beta receptor type I TLR4 Tiam1 c-Src p19 p21 10 Cell Differentiation Angiogenesis 5-AZA 5-AZA+MS-275 5-AZA 5-AZA+MS-275 P-value: 1.2 x 10-8 P-value: 7.2 x 10-3 P-value: 2.5 x 10-2 P-value: 1.5 x 10-2 AKT(PKB) ADAM17 AKT(PKB) ADAM17 ActRIIA AKT(PKB) AL3A1 AKT(PKB) Activin A Adenylate cyclase CALDAG-GEFI AL3A1 Alpha1-globin Alpha1-globin CCL2 Adenylate cyclase type III Bcl-XL Angiotensin II COX-2 (PTGS2) Brca1 C/EBPbeta Aurora-A DDC G-protein alpha-i family CCL2 Bax Fyn HEY1 CLF-1 CDC20 G-protein beta/gamma HIF-prolyl hydroxylase COX-2 (PTGS2) CDK1 (p34) HDAC2 HSP70 CXCR4 CYP2C9 HEY1 Heme oxygenase 1 CYP2B6 Cyclin B1 HIF-prolyl hydroxylase MMP-9 Chromogranin A Cyclin D1 HSP70 PDGF receptor Collagen II Cyclin D3 IP3 receptor PDGF-R-alpha Cyclin D3 DHRS4 MEK1(MAP2K1) PKC DHA6 E-cadherin MEK1/2 SPHK1 EDG3 Ephrin-B MMP-14 Survivin EDG5 G-protein alpha-i MMP-9 Syndecan-4 family ER81 GRK3 PKA-cat (cAMP- Tiam1 dependent) Ephrin-B Galpha(q)-specific PKA-cat alpha VEGF-A frizzled GPCRs Ephrin-B receptors HEY1 PLC-beta VEGF-C FAP-1 HSP70 PLGF Vitronectin Fyn Hck Protein kinase G c-Fos G-protein beta/gamma Kinase MYT1 Protein kinase G1 c-Src alpha GFRalpha2 LIPS RAP-1A p21 GH-RH receptor Lyn TLE p38 MAPK HDAC2 MMP-9 Tiam1 11 Cell Differentiation Angiogenesis 5-AZA 5-AZA+MS-275 5-AZA 5-AZA+MS-275 P-value: 1.2 x 10-8 P-value: 7.2 x 10-3 P-value: 2.5 x 10-2 P-value: 1.5 x 10-2 HEY1 PDGF receptor VEGF-C HMGA2 PDGF-R-alpha Vitronectin
Recommended publications
  • Defining Functional Interactions During Biogenesis of Epithelial Junctions

    Defining Functional Interactions During Biogenesis of Epithelial Junctions

    ARTICLE Received 11 Dec 2015 | Accepted 13 Oct 2016 | Published 6 Dec 2016 | Updated 5 Jan 2017 DOI: 10.1038/ncomms13542 OPEN Defining functional interactions during biogenesis of epithelial junctions J.C. Erasmus1,*, S. Bruche1,*,w, L. Pizarro1,2,*, N. Maimari1,3,*, T. Poggioli1,w, C. Tomlinson4,J.Lees5, I. Zalivina1,w, A. Wheeler1,w, A. Alberts6, A. Russo2 & V.M.M. Braga1 In spite of extensive recent progress, a comprehensive understanding of how actin cytoskeleton remodelling supports stable junctions remains to be established. Here we design a platform that integrates actin functions with optimized phenotypic clustering and identify new cytoskeletal proteins, their functional hierarchy and pathways that modulate E-cadherin adhesion. Depletion of EEF1A, an actin bundling protein, increases E-cadherin levels at junctions without a corresponding reinforcement of cell–cell contacts. This unexpected result reflects a more dynamic and mobile junctional actin in EEF1A-depleted cells. A partner for EEF1A in cadherin contact maintenance is the formin DIAPH2, which interacts with EEF1A. In contrast, depletion of either the endocytic regulator TRIP10 or the Rho GTPase activator VAV2 reduces E-cadherin levels at junctions. TRIP10 binds to and requires VAV2 function for its junctional localization. Overall, we present new conceptual insights on junction stabilization, which integrate known and novel pathways with impact for epithelial morphogenesis, homeostasis and diseases. 1 National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London SW7 2AZ, UK. 2 Computing Department, Imperial College London, London SW7 2AZ, UK. 3 Bioengineering Department, Faculty of Engineering, Imperial College London, London SW7 2AZ, UK. 4 Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, London SW7 2AZ, UK.
  • Absence of NEFL in Patient-Specific Neurons in Early-Onset Charcot-Marie-Tooth Neuropathy Markus T

    Absence of NEFL in Patient-Specific Neurons in Early-Onset Charcot-Marie-Tooth Neuropathy Markus T

    ARTICLE OPEN ACCESS Absence of NEFL in patient-specific neurons in early-onset Charcot-Marie-Tooth neuropathy Markus T. Sainio, MSc, Emil Ylikallio, MD, PhD, Laura M¨aenp¨a¨a, MSc, Jenni Lahtela, PhD, Pirkko Mattila, PhD, Correspondence Mari Auranen, MD, PhD, Johanna Palmio, MD, PhD, and Henna Tyynismaa, PhD Dr. Tyynismaa [email protected] Neurol Genet 2018;4:e244. doi:10.1212/NXG.0000000000000244 Abstract Objective We used patient-specific neuronal cultures to characterize the molecular genetic mechanism of recessive nonsense mutations in neurofilament light (NEFL) underlying early-onset Charcot- Marie-Tooth (CMT) disease. Methods Motor neurons were differentiated from induced pluripotent stem cells of a patient with early- onset CMT carrying a novel homozygous nonsense mutation in NEFL. Quantitative PCR, protein analytics, immunocytochemistry, electron microscopy, and single-cell transcriptomics were used to investigate patient and control neurons. Results We show that the recessive nonsense mutation causes a nearly total loss of NEFL messenger RNA (mRNA), leading to the complete absence of NEFL protein in patient’s cultured neurons. Yet the cultured neurons were able to differentiate and form neuronal networks and neuro- filaments. Single-neuron gene expression fingerprinting pinpointed NEFL as the most down- regulated gene in the patient neurons and provided data of intermediate filament transcript abundancy and dynamics in cultured neurons. Blocking of nonsense-mediated decay partially rescued the loss of NEFL mRNA. Conclusions The strict neuronal specificity of neurofilament has hindered the mechanistic studies of re- cessive NEFL nonsense mutations. Here, we show that such mutation leads to the absence of NEFL, causing childhood-onset neuropathy through a loss-of-function mechanism.
  • Map2k1 and Map2k2 Genes Contribute to the Normal Development of Syncytiotrophoblasts During Placentation

    Map2k1 and Map2k2 Genes Contribute to the Normal Development of Syncytiotrophoblasts During Placentation

    RESEARCH ARTICLE 1363 Development 136, 1363-1374 (2009) doi:10.1242/dev.031872 Map2k1 and Map2k2 genes contribute to the normal development of syncytiotrophoblasts during placentation Valérie Nadeau*, Stéphanie Guillemette*, Louis-François Bélanger, Olivier Jacob, Sophie Roy and Jean Charron† The mammalian genome contains two ERK/MAP kinase kinase genes, Map2k1 and Map2k2, which encode dual-specificity kinases responsible for ERK/MAP kinase activation. In the mouse, loss of Map2k1 function causes embryonic lethality, whereas Map2k2 mutants survive with a normal lifespan, suggesting that Map2k1 masks the phenotype due to the Map2k2 mutation. To uncover the specific function of MAP2K2 and the threshold requirement of MAP2K proteins during embryo formation, we have successively ablated the Map2k gene functions. We report here that Map2k2 haploinsufficiency affects the normal development of placenta in the absence of one Map2k1 allele. Most Map2k1+/–Map2k2+/– embryos die during gestation because of placenta defects restricted to extra-embryonic tissues. The impaired viability of Map2k1+/–Map2k2+/– embryos can be rescued when the Map2k1 deletion is restricted to the embryonic tissues. The severity of the placenta phenotype is dependent on the number of Map2k mutant alleles, the deletion of the Map2k1 allele being more deleterious. Moreover, the deletion of one or both Map2k2 alleles in the context of one null Map2k1 allele leads to the formation of multinucleated trophoblast giant (MTG) cells. Genetic experiments indicate that these structures are derived from Gcm1-expressing syncytiotrophoblasts (SynT), which are affected in their ability to form the uniform SynT layer II lining the maternal sinuses. Thus, even though Map2k1 plays a predominant role, these results enlighten the function of Map2k2 in placenta development.
  • The Genetic Landscape of Clinical Resistance to RAF Inhibition in Metastatic Melanoma

    The Genetic Landscape of Clinical Resistance to RAF Inhibition in Metastatic Melanoma

    CD-13-0617_PAP.indd Page OF1 19/11/13 9:36 PM user-f028 /Books-Arts/JOURNAL-Cancer%20Discovery/01-JAN-Issue-2014/PAP Published OnlineFirst November 21, 2013; DOI: 10.1158/2159-8290.CD-13-0617 RESEARCH ARTICLE The Genetic Landscape of Clinical Resistance to RAF Inhibition in Metastatic Melanoma Eliezer M. Van Allen 1 , 3 , Nikhil Wagle 1 , 3 , Antje Sucker 5 , 6 , Daniel J. Treacy 1 , Cory M. Johannessen 3 , Eva M. Goetz 1 , Chelsea S. Place 1 , 3 , Amaro Taylor-Weiner 3 , Steven Whittaker 3 , Gregory V. Kryukov 3 , Eran Hodis 1 , 3,4 , Mara Rosenberg 3 , Aaron McKenna 3 , 15 , Kristian Cibulskis 3 , Deborah Farlow 3 , Lisa Zimmer 5 , 6 , Uwe Hillen 5 , 6 , Ralf Gutzmer 8 , Simone M. Goldinger 16 , Selma Ugurel 9 , Helen J. Gogas 17 , Friederike Egberts 10 , Carola Berking 6 , 11 , Uwe Trefzer 6 , 12 , Carmen Loquai 6 , 13 , Benjamin Weide 6 , 14 , Jessica C. Hassel 6 , 7 , Stacey B. Gabriel 3 , Scott L. Carter 3 , Gad Getz 2 , 3 , Levi A. Garraway 1 , 3 , and Dirk Schadendorf 5 , 6 on behalf of the Dermatologic Cooperative Oncology Group of Germany (DeCOG) Downloaded from cancerdiscovery.aacrjournals.org on September 25, 2021. © 2013 American Association for Cancer Research. CD-13-0617_PAP.indd Page OF2 19/11/13 9:36 PM user-f028 /Books-Arts/JOURNAL-Cancer%20Discovery/01-JAN-Issue-2014/PAP Published OnlineFirst November 21, 2013; DOI: 10.1158/2159-8290.CD-13-0617 ABSTRACT Most patients with BRAF V600 -mutant metastatic melanoma develop resistance to selective RAF kinase inhibitors. The spectrum of clinical genetic resistance mechanisms to RAF inhibitors and options for salvage therapy are incompletely understood.
  • Serum Albumin OS=Homo Sapiens

    Serum Albumin OS=Homo Sapiens

    Protein Name Cluster of Glial fibrillary acidic protein OS=Homo sapiens GN=GFAP PE=1 SV=1 (P14136) Serum albumin OS=Homo sapiens GN=ALB PE=1 SV=2 Cluster of Isoform 3 of Plectin OS=Homo sapiens GN=PLEC (Q15149-3) Cluster of Hemoglobin subunit beta OS=Homo sapiens GN=HBB PE=1 SV=2 (P68871) Vimentin OS=Homo sapiens GN=VIM PE=1 SV=4 Cluster of Tubulin beta-3 chain OS=Homo sapiens GN=TUBB3 PE=1 SV=2 (Q13509) Cluster of Actin, cytoplasmic 1 OS=Homo sapiens GN=ACTB PE=1 SV=1 (P60709) Cluster of Tubulin alpha-1B chain OS=Homo sapiens GN=TUBA1B PE=1 SV=1 (P68363) Cluster of Isoform 2 of Spectrin alpha chain, non-erythrocytic 1 OS=Homo sapiens GN=SPTAN1 (Q13813-2) Hemoglobin subunit alpha OS=Homo sapiens GN=HBA1 PE=1 SV=2 Cluster of Spectrin beta chain, non-erythrocytic 1 OS=Homo sapiens GN=SPTBN1 PE=1 SV=2 (Q01082) Cluster of Pyruvate kinase isozymes M1/M2 OS=Homo sapiens GN=PKM PE=1 SV=4 (P14618) Glyceraldehyde-3-phosphate dehydrogenase OS=Homo sapiens GN=GAPDH PE=1 SV=3 Clathrin heavy chain 1 OS=Homo sapiens GN=CLTC PE=1 SV=5 Filamin-A OS=Homo sapiens GN=FLNA PE=1 SV=4 Cytoplasmic dynein 1 heavy chain 1 OS=Homo sapiens GN=DYNC1H1 PE=1 SV=5 Cluster of ATPase, Na+/K+ transporting, alpha 2 (+) polypeptide OS=Homo sapiens GN=ATP1A2 PE=3 SV=1 (B1AKY9) Fibrinogen beta chain OS=Homo sapiens GN=FGB PE=1 SV=2 Fibrinogen alpha chain OS=Homo sapiens GN=FGA PE=1 SV=2 Dihydropyrimidinase-related protein 2 OS=Homo sapiens GN=DPYSL2 PE=1 SV=1 Cluster of Alpha-actinin-1 OS=Homo sapiens GN=ACTN1 PE=1 SV=2 (P12814) 60 kDa heat shock protein, mitochondrial OS=Homo
  • Nerve Growth Factor Induces Transcription of the P21 WAF1/CIP1 and Cyclin D1 Genes in PC12 Cells by Activating the Sp1 Transcription Factor

    Nerve Growth Factor Induces Transcription of the P21 WAF1/CIP1 and Cyclin D1 Genes in PC12 Cells by Activating the Sp1 Transcription Factor

    The Journal of Neuroscience, August 15, 1997, 17(16):6122–6132 Nerve Growth Factor Induces Transcription of the p21 WAF1/CIP1 and Cyclin D1 Genes in PC12 Cells by Activating the Sp1 Transcription Factor Guo-Zai Yan and Edward B. Ziff Howard Hughes Medical Institute, Department of Biochemistry, Kaplan Cancer Center, New York University Medical Center, New York, New York 10016 The PC12 pheochromocytoma cell line responds to nerve in which the Gal4 DNA binding domain is fused to the Sp1 growth factor (NGF) by gradually exiting from the cell cycle and transactivation domain, indicating that this transactivation do- differentiating to a sympathetic neuronal phenotype. We have main is regulated by NGF. Epidermal growth factor, which is a shown previously (Yan and Ziff, 1995) that NGF induces the weak mitogen for PC12, failed to induce any of these promoter expression of the p21 WAF1/CIP1/Sdi1 (p21) cyclin-dependent constructs. We consider a model in which the PC12 cell cycle kinase (Cdk) inhibitor protein and the G1 phase cyclin, cyclin is arrested as p21 accumulates and attains inhibitory levels D1. In this report, we show that induction is at the level of relative to Cdk/cyclin complexes. Sustained activation of p21 transcription and that the DNA elements in both promoters that expression is proposed to be a distinguishing feature of the are required for NGF-specific induction are clusters of binding activity of NGF that contributes to PC12 growth arrest during sites for the Sp1 transcription factor. NGF also induced a differentiation synthetic
  • Role of Cyclin-Dependent Kinase 1 in Translational Regulation in the M-Phase

    Role of Cyclin-Dependent Kinase 1 in Translational Regulation in the M-Phase

    cells Review Role of Cyclin-Dependent Kinase 1 in Translational Regulation in the M-Phase Jaroslav Kalous *, Denisa Jansová and Andrej Šušor Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, Rumburska 89, 27721 Libechov, Czech Republic; [email protected] (D.J.); [email protected] (A.Š.) * Correspondence: [email protected] Received: 28 April 2020; Accepted: 24 June 2020; Published: 27 June 2020 Abstract: Cyclin dependent kinase 1 (CDK1) has been primarily identified as a key cell cycle regulator in both mitosis and meiosis. Recently, an extramitotic function of CDK1 emerged when evidence was found that CDK1 is involved in many cellular events that are essential for cell proliferation and survival. In this review we summarize the involvement of CDK1 in the initiation and elongation steps of protein synthesis in the cell. During its activation, CDK1 influences the initiation of protein synthesis, promotes the activity of specific translational initiation factors and affects the functioning of a subset of elongation factors. Our review provides insights into gene expression regulation during the transcriptionally silent M-phase and describes quantitative and qualitative translational changes based on the extramitotic role of the cell cycle master regulator CDK1 to optimize temporal synthesis of proteins to sustain the division-related processes: mitosis and cytokinesis. Keywords: CDK1; 4E-BP1; mTOR; mRNA; translation; M-phase 1. Introduction 1.1. Cyclin Dependent Kinase 1 (CDK1) Is a Subunit of the M Phase-Promoting Factor (MPF) CDK1, a serine/threonine kinase, is a catalytic subunit of the M phase-promoting factor (MPF) complex which is essential for cell cycle control during the G1-S and G2-M phase transitions of eukaryotic cells.
  • Personalized Prediction of Acquired Resistance to EGFR-Targeted Inhibitors Using a Pathway-Based Machine Learning Approach

    Personalized Prediction of Acquired Resistance to EGFR-Targeted Inhibitors Using a Pathway-Based Machine Learning Approach

    Cancers 2019, 11, x S1 of S9 Supplementary Materials: Personalized Prediction of Acquired Resistance to EGFR-Targeted Inhibitors Using a Pathway-Based Machine Learning Approach Young Rae Kim, Yong Wan Kim, Suh Eun Lee, Hye Won Yang and Sung Young Kim Table S1. Characteristics of individual studies. Sample Size Origin of Cancer Drug Dataset Platform S AR (Cell Lines) Lung cancer Agilent-014850 Whole Human GSE34228 26 26 (PC9) Genome Microarray 4x44K Gefitinib Epidermoid carcinoma Affymetrix Human Genome U133 GSE10696 3 3 (A431) Plus 2.0 Head and neck cancer Illumina HumanHT-12 V4.0 GSE62061 12 12 (Cal-27, SSC-25, FaDu, expression beadchip SQ20B) Erlotinib Head and neck cancer Illumina HumanHT-12 V4.0 GSE49135 3 3 (HN5) expression beadchip Lung cancer (HCC827, Illumina HumanHT-12 V3.0 GSE38310 3 6 ER3, T15-2) expression beadchip Lung cancer Illumina HumanHT-12 V3.0 GSE62504 1 2 (HCC827) expression beadchip Afatinib Lung cancer * Illumina HumanHT-12 V4.0 GSE75468 1 3 (HCC827) expression beadchip Head and neck cancer Affymetrix Human Genome U133 Cetuximab GSE21483 3 3 (SCC1) Plus 2.0 Array GEO, gene expression omnibus; GSE, gene expression series; S, sensitive; AR, acquired EGFR-TKI resistant; * Lung Cancer Cells Derived from Tumor Xenograft Model. Table S2. The performances of four penalized regression models. Model ACC precision recall F1 MCC AUROC BRIER Ridge 0.889 0.852 0.958 0.902 0.782 0.964 0.129 Lasso 0.944 0.957 0.938 0.947 0.889 0.991 0.042 Elastic Net 0.978 0.979 0.979 0.979 0.955 0.999 0.023 EPSGO Elastic Net 0.989 1.000 0.979 0.989 0.978 1.000 0.018 AUROC, area under curve of receiver operating characteristic; ACC, accuracy; MCC, Matthews correlation coefficient; EPSGO, Efficient Parameter Selection via Global Optimization algorithm.
  • Spatial Distribution of Leading Pacemaker Sites in the Normal, Intact Rat Sinoa

    Spatial Distribution of Leading Pacemaker Sites in the Normal, Intact Rat Sinoa

    Supplementary Material Supplementary Figure 1: Spatial distribution of leading pacemaker sites in the normal, intact rat sinoatrial 5 nodes (SAN) plotted along a normalized y-axis between the superior vena cava (SVC) and inferior vena 6 cava (IVC) and a scaled x-axis in millimeters (n = 8). Colors correspond to treatment condition (black: 7 baseline, blue: 100 µM Acetylcholine (ACh), red: 500 nM Isoproterenol (ISO)). 1 Supplementary Figure 2: Spatial distribution of leading pacemaker sites before and after surgical 3 separation of the rat SAN (n = 5). Top: Intact SAN preparations with leading pacemaker sites plotted during 4 baseline conditions. Bottom: Surgically cut SAN preparations with leading pacemaker sites plotted during 5 baseline conditions (black) and exposure to pharmacological stimulation (blue: 100 µM ACh, red: 500 nM 6 ISO). 2 a &DUGLDFIoQChDQQHOV .FQM FOXVWHU &DFQDG &DFQDK *MD &DFQJ .FQLS .FQG .FQK .FQM &DFQDF &DFQE .FQM í $WSD .FQD .FQM í .FQN &DVT 5\U .FQM &DFQJ &DFQDG ,WSU 6FQD &DFQDG .FQQ &DFQDJ &DFQDG .FQD .FQT 6FQD 3OQ 6FQD +FQ *MD ,WSU 6FQE +FQ *MG .FQN .FQQ .FQN .FQD .FQE .FQQ +FQ &DFQDD &DFQE &DOP .FQM .FQD .FQN .FQG .FQN &DOP 6FQD .FQD 6FQE 6FQD 6FQD ,WSU +FQ 6FQD 5\U 6FQD 6FQE 6FQD .FQQ .FQH 6FQD &DFQE 6FQE .FQM FOXVWHU V6$1 L6$1 5$ /$ 3 b &DUGLDFReFHSWRUV $GUDF FOXVWHU $GUDD &DY &KUQE &KUP &KJD 0\O 3GHG &KUQD $GUE $GUDG &KUQE 5JV í 9LS $GUDE 7SP í 5JV 7QQF 3GHE 0\K $GUE *QDL $QN $GUDD $QN $QN &KUP $GUDE $NDS $WSE 5DPS &KUP 0\O &KUQD 6UF &KUQH $GUE &KUQD FOXVWHU V6$1 L6$1 5$ /$ 4 c 1HXURQDOPURWHLQV
  • Correction1 4784..4785

    Correction1 4784..4785

    Correction Correction: PCI-24781 Induces Caspase and Reactive Oxygen Species-Dependent Apoptosis In the article on PCI-24781 induces caspase and reactive oxygen species-dependent apoptosis published in the May 15, 2009 issue of Clinical Cancer Research, there was an error in Table 1. Down-regulated genes were incorrectly labeled as up-regulated genes. The correct table appears here. Bhalla S, Balasubramanian S, David K, et al. PCI-24781 induces caspase and reactive oxygen species-dependent apoptosis through NF-nB mechanisms and is synergistic with bortezomib in lymphoma cells. Clin Cancer Res 2009;15:3354–65. Table 1. Selected genes from expression analysis following 24-h treatment with PCI-24781, bortezomib, or the combination (in Ramos cells) Accn # Down-regulated genes 0.25 Mmol/L PCI/3 nmol/L Bor Name PCI-24781 Bortezomib Combination* Cell cycle-related NM_000075 Cyclin-dependent kinase 4 (CDK4) 0.49 0.83 0.37 NM_001237 Cyclin A2 (CCNA2) 0.43 0.87 0.37 NM_001950 E2F transcription factor 4, p107/p130-binding (E2F4) 0.48 0.79 0.40 NM_001951 E2F transcription factor 5, p130-binding (E2F5) 0.46 0.98 0.43 NM_003903 CDC16 cell division cycle 16 homolog (S cerevisiae) (CDC16) 0.61 0.78 0.43 NM_031966 Cyclin B1 (CCNB1) 0.55 0.90 0.43 NM_001760 Cyclin D3 (CCND3) 0.48 1.02 0.46 NM_001255 CDC20 cell division cycle 20 homolog (S cerevisiae; CDC20) 0.61 0.82 0.46 NM_001262 Cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4; CDKN2C) 0.61 1.15 0.56 NM_001238 Cyclin E1 (CCNE1) 0.56 1.05 0.60 NM_001239 Cyclin H (CCNH) 0.74 0.90 0.64 NM_004701
  • The Localization of Human Cyclins B1 and B2 Determines CDK1

    The Localization of Human Cyclins B1 and B2 Determines CDK1

    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by PubMed Central The Localization of Human Cyclins B1 and B2 Determines CDK1 Substrate Specificity and Neither Enzyme Requires MEK to Disassemble the Golgi Apparatus Viji Mythily Draviam,* Simona Orrechia,‡ Martin Lowe,§ Ruggero Pardi,‡ and Jonathon Pines* *Wellcome/Cancer Research Campaign Institute and Department of Zoology, Cambridge CB2 1QR, United Kingdom; ‡Vita Salute University School of Medicine, Scientific Institute San Raffaele, Milan I-20132, Italy; and §Division of Biochemistry, School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom Abstract. In this paper, we show that substrate specificity confer upon it the more limited properties of cyclin B2. is primarily conferred on human mitotic cyclin-dependent Equally, directing cyclin B2 to the cytoplasm with the kinases (CDKs) by their subcellular localization. The NH2 terminus of cyclin B1 confers the broader properties difference in localization of the B-type cyclin–CDKs of cyclin B1. Furthermore, we show that the disassembly underlies the ability of cyclin B1–CDK1 to cause chromo- of the Golgi apparatus initiated by either mitotic cyclin– some condensation, reorganization of the microtubules, CDK complex does not require mitogen-activated and disassembly of the nuclear lamina and of the Golgi protein kinase kinase (MEK) activity. apparatus, while it restricts cyclin B2–CDK1 to disassem- bly of the Golgi apparatus. We identify the region of Key words: cyclin • CDK • mitosis • protein kinase • cyclin B2 responsible for its localization and show that Golgi apparatus this will direct cyclin B1 to the Golgi apparatus and Introduction Cyclins play a vital role in controlling progress through the or mitosis (M phase) depending on the amount of kinase eukaryotic cell cycle.
  • Characterization of the Small Molecule Kinase Inhibitor SU11248 (Sunitinib/ SUTENT in Vitro and in Vivo

    Characterization of the Small Molecule Kinase Inhibitor SU11248 (Sunitinib/ SUTENT in Vitro and in Vivo

    TECHNISCHE UNIVERSITÄT MÜNCHEN Lehrstuhl für Genetik Characterization of the Small Molecule Kinase Inhibitor SU11248 (Sunitinib/ SUTENT in vitro and in vivo - Towards Response Prediction in Cancer Therapy with Kinase Inhibitors Michaela Bairlein Vollständiger Abdruck der von der Fakultät Wissenschaftszentrum Weihenstephan für Ernährung, Landnutzung und Umwelt der Technischen Universität München zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften genehmigten Dissertation. Vorsitzender: Univ. -Prof. Dr. K. Schneitz Prüfer der Dissertation: 1. Univ.-Prof. Dr. A. Gierl 2. Hon.-Prof. Dr. h.c. A. Ullrich (Eberhard-Karls-Universität Tübingen) 3. Univ.-Prof. A. Schnieke, Ph.D. Die Dissertation wurde am 07.01.2010 bei der Technischen Universität München eingereicht und durch die Fakultät Wissenschaftszentrum Weihenstephan für Ernährung, Landnutzung und Umwelt am 19.04.2010 angenommen. FOR MY PARENTS 1 Contents 2 Summary ................................................................................................................................................................... 5 3 Zusammenfassung .................................................................................................................................................... 6 4 Introduction .............................................................................................................................................................. 8 4.1 Cancer ..............................................................................................................................................................