DOCSLIB.ORG

Supplemental Table (PDF File, 156Kb)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Supplemental Table (PDF File, 156Kb) Supplementary Information Table 1. Catalogue of homologs to immune-related genes in Chinese amphioxus. ID Similarity to Species Accession no. Function Genes may be involved in rearrangement 1132 Karyopherin alpha 2/RAG cohort 1 Homo sapiens AAH53343.1 V(D)J recombination, nuclear transport of proteins 2806 recombination activating gene 1 Mus musculus NP_033083.1 Putatively involved in activation and expression gene activation, recombination of recombination activation genes (RAGs). activating gene 1 inducing protein Genes of immunoglobulin superfamily 2234 Variable region-containing Branchiostoma AAN62910.1 IgSF like protein chitin-binding protein 4 floridae 2372 T cell receptor V delta 2 Rattus norvegicus AF196201_1 IgSF like protein Genes controlling lymphocyte ontogeny 1367 Max dimerization protein Mus musculus NP_034881.1 another basic helix-loop-helix protein that binds to MYC and is required for its function. 1368 max interacting protein 1 Rattus norvegicus NP_037292.1 HLH protein that binds to MYC 1809 receptor protein Notch1 Cynops BAC 41349.1 a receptor for membrane bound ligands, and may pyrrhogaster play multiple roles during development 2890 MYC PROTEIN (C-MYC) pir; Homo sapiens Q17103 v-myc myelocytomatosis viral related oncogene, neuroblastoma derived 3767 Myb-like DNA-binding domain Mus musculus BAB22140.1 Regulate the expression of CD34,CD13, c-myc, containing protein cdc2, CD4,TCR 898 ETS homologue Strongylocentrotus AAA30048.1 Transcription factor purpuratus 4966 early B-cell factor 3; Olf-1/EBF-like Mus musculus NP_034226.1 early B-cell development 2 6151 Myc homolog Crassostrea AAB34577.1 Expression of the c-myc, produces an oncogenic virginica transcription factor, is regulated in normal cells but is frequently deregulated in human cancers. 6296 interferon regulatory factor 2 Homo sapiens AAH15803 inhibits the IRF1-mediated transcriptional activation of interferons alpha and beta 6655 Notch homolog protein sea squirt T30201 as a receptor for membrane bound ligands, and (Halocynthia may play multiple roles during development roretzi) Genes involved in lymphocyte signaling 25 CD63 antigen; melanoma 1 antigen Mus musculus NP_031679.1 Tetraspanin receptors, participation in cell migration and adhesion 354 casein kinase I alpha LS Gallus gallus AAB96334.1 cell surface receptor linked signal transduction ID Similarity to Species Accession no. Function 525 RAN_BRARE GTP-BINDING Danio rerio P79735 GTP-binding protein NUCLEAR PROTEIN RAN 535 Activated protein kinase C receptor Rattus norvegicus A36986 PRKC-mediated signaling (RACK1) 1187 ras homolog gene family, member Homo sapiens NP_001655.1 Rho protein signal transduction A; GTP-binding protein 1206 mitogen-activated protein kinase Homo sapiens NP_002749.2 mitogen-activated protein (MAP) kinase kinase kinase 6 isoform 1 1600 ADP-ribosylation factor-like 2 Homo sapiens AAH02530 small GTP-binding proteins of the RAS superfamily 1857 Protein tyrosine phosphatase IVA1 Homo sapiens NP_003454.1 Protein tyrosine phosphatase 2195 Leukocyte surface antigen CD53 Mus musculus NP_031677.1 transduction of CD2-generated signals in T cells and natural killer cells 2236 tumor necrosis factor alpha induced Mus musculus NP_033424.1 Hyaluronan-binding protein protein 6 2368 Tumor necrosis factor Homo sapiens AAD24202 intracellular trafficking receptor-associated factor 4(TRAF4)-associated factor 2 2723 tumor necrosis factor alpha induced Mus musculus NP_033424.1 Hyaluronan-binding protein protein 6 4229 mitogen activated protein kinase Mus musculus NP_035970.1 growth factor stimulated cell proliferation and kinase 5 muscle cell differentiation. 4530 CD3 associated protein; antisense Homo sapiens AF017633_1 T-cell activation to ERCC-1 (CAST) 5104 Casein kinase II, alpha chain Homo sapiens P21868 Actin binding 5404 mitogen-activated protein kinase 10 Homo sapiens NP_002744.1 plays regulatory roles in the signaling pathways isoform 1 during neuronal apoptosis 5661 TNF receptor associated factor 3 Mus musculus AAC52175.1 a critical component of the lymphotoxin-beta (CD40 receptor associated factor 1) receptor (LTbetaR) signaling complex 5977 B cell phosphoinositide 3-kinase Petromyzon AAN64296.2 Links BCR-associated kinases with adaptor (BCAP) marinus phosphatidylinositol 3-kinase 6024 pre-B-cell colony-enhancing factor Suberites CAB65409.1 up-regulated in activated lymphocytes, domuncula nicotinamide phosphoribosyltransferase 6570 LPS-induced TNF-alpha factor Mus musculus NP_064364.1 small integral membrane protein of lysosome/late endosome 6827 kangai 1,CD82 antigen Rattus norvegicus NP_113985.1 metastasis suppressor Genes required for lymphocyte proliferation and migration 1492 CD81 antigen (target of Rattus norvegicus NP_037219.1 Tetraspanin receptors, participation in cell antiproliferative antibody 1) migration and adhesion 3308 CD9 antigen Sus scrofa Q8WMQ3 Tetraspanin receptors, participation in cell migration and adhesion Genes involving in antigen processing and ID Similarity to Species Accession no. Function presentation 221 proteasome (prosome, macropain) Mus musculus NP_036098.1 Protein degradation subunit, alpha type 6, PSMA6 484 HLA-B-associated transcript 1A Homo sapiens AAB94615.1 DEAD protein family of ATP-dependent RNA helicases 512 ribosome associated membrane Homo sapiens AAH29067.1 Controls glycosylation of MHC class protein 4 II-associated invariant chain 676 proteasome (prosome, macropain) Homo sapiens AAP88811.1 Protein degradation subunit, beta type, 6 PSMB6 972 interferon gamma inducible; Mus musculus NP_075552.1 MHC class II-restricted antigen processing lysosomal thiol reductase protein 30 988 allograft inflammatory factor 1 Suberites CAC38780.1 ionized calcium binding adapter domuncula 1082 calreticulin Mus musculus NP_031617.1 major Ca(2+)-binding (storage) protein 1100 proteosome PSMB5/8 protein Branchiostoma AAL74417.1 Protein degradation lanceolatum 1467 nuclear factor of kappa light Mus musculus NP_035039.1 unknown, Lies in MHC class I region polypeptide gene enhancer in B-cells inhibitor-like 1 1628 proteasome (prosome, macropain) Homo sapiens AAH00509 Protein degradation subunit, beta type, 7 , PSMB7 2255 cathepsin L Sus scrofa CAC44793.1 Cysteine protease 2438 Cathepsin B precursor Araneus AAP59456.1 Cysteine protease ventricosus 2776 cathepsin Z Mus musculus CAB44494.1 Cysteine protease 3311 HLA class II region expressed gene Homo sapiens NP_055075.1 chaperone activity, Lies in MHC region KE2 3316 cathepsin D Apriona germari AF454831_1 Cysteine protease 3349 heat shock protein hsp70-related Homo sapiens NP_057383.1 Chaperone protein 4667 source of immunodominant Homo sapiens AAL71884.1 oligosaccharyl transferase activity MHC-associated peptides 5021 IK cytokine, down-regulator of HLA Mus musculus XP_128899.1 down-regulate HLA II molecular II 5552 novel protein similar to Danio rerio CAD54662.1 Lies in MHC region hydroxysteroid (17-beta) dehydrogenase 8, RING2 (KE6) 6292 ABC-C transporter Homo sapiens CAA65825.1 ABC transporter 6935 HLA-B associated transcript 5 Homo sapiens NP_066983 involved in some aspects of immunity. Other immune-related genes 190 peptidylprolyl isomerase-like 1 Mus musculus NP_081121.1 Binds cyclosporin A 839 chaperonin containing TCP1, Homo sapiens NP_006420.1 chaperone activity ID Similarity to Species Accession no. Function subunit 7 (eta); chaperonin containing t-complex polypeptide 1, eta subunit 840 chaperonin-containing T-complex Danio rerio AF506229_1 chaperone activity protein 1 zeta subunit 873 90 kDa heat-shock protein Homo sapiens CAA33259.1 Chaperone 1613 macrophage migration inhibitory Amblyomma AF126688_1 Regulation of macrophage function in factor americanum inflammation 1930 peptidylprolyl isomerase-like 3; Mus musculus NP_081627.1 Binds cyclosporin A cyclophilin-like 3 2586 mature T-cell proliferation 1 Mus musculus NP_034969.1 mature T cell proliferation 2813 mitogen-activated protein-binding Mus musculus NP_112538.1 late endosomal/lysosomal MP1 interacting protein-interacting protein protein 3086 T-complex protein 1, zeta subunit Oryctolagus AAC19379.1 chaperone activity, cytoplasm (TCP-1-zeta) (CCT-zeta) cuniculus 3245 DnaJ (Hsp40) homolog, subfamily Mus musculus NP_032324.1 Chaperone A, member 1 3297 dnaK-type molecular chaperone Dictyostelium S37394 Chaperone hsc70 discoideum 3555 peptidyl prolyl isomerase H; Homo sapiens NP_006338.1 Binds cyclosporin A cyclophilin H 3905 basic, immunoglobulin-like variable Strongylocentrotus AF411391_1 immunoglobulin-like variable motif-containing motif-containing protein purpuratus protein 4462 TGF-beta receptor binding protein Mus musculus XP_216619.1 translation initiation factor activity 5132 ferritin Branchiostoma AAN77903.1 Iron storage and cellular regulation belcheri 5445 Chaperone protein dnaK Porphyromonas BAA35087.1 Chaperone gingivalis 5709 Alpha-2-macroglobulin Mus musculus NP_783327.1 protease inhibitor and cytokine transporter 5748 paired box protein Pax-2 beta Branchiostoma AAC12734.1 critical regulators that specify the nephric isoform floridae lineage. 6160 B lymphocyte cell adhesion Mus musculus AF102134_1 cell adhesion molecule activity molecule, CD22 antigen 6232 dendritic cells-lysosome associated Mus musculus CAD52824.1 provides selectins with carbohydrate ligands membrane glycoprotein 6779 Thioredoxin Branchiostoma AAK72483.1 Redox reactions, augments expression of IL-2 belcheri receptor 7056 natural killer cell enhancement Oncorhynchus AF250193_1 Immunoregulation of natural killer cell activity factor mykiss 242 Peptidyl-prolyl cis-trans
Load more

Recommended publications
  • In Vitro Differentiation of Bone Marrow Mesenchymal Stem Cells Into Endometrial Epithelial Cells in Mouse: a Proteomic Analysis
    Int J Clin Exp Pathol 2014;7(7):3662-3672 www.ijcep.com /ISSN:1936-2625/IJCEP0000322 Original Article In vitro differentiation of bone marrow mesenchymal stem cells into endometrial epithelial cells in mouse: a proteomic analysis Qing Cong1,2, Bin Li1,2, Yisheng Wang1,2, Wenbi Zhang1,2, Mingjun Cheng1,2, Zhiyong Wu1,2, Xiaoyan Zhang1,2, Wei Jiang1,2, Congjian Xu1,2,3,4 1Obstetrics and Gynecology Hospital of Fudan University, 2Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, 3Department of Obstetrics and Gynecology of Shanghai Medical School, 4Institute of Biomedical Sciences, Fudan University, Shanghai, P.R. China Received March 24, 2014; Accepted June 23, 2014; Epub June 15, 2014; Published July 1, 2014 Abstract: Objective: Mouse bone marrow mesenchymal stem cells (BMSCs) have been demonstrated to differenti- ate into female endometrial epithelial cells (EECs) in vivo. Our previous studies demonstrated that BMSCs can differentiate in the direction of EECs when co-cultured with endometrial stromal cells in vitro. Here, we obtain and analyse differential proteins and their relevant pathways in the process of BMSCs differentiating into EECs by iso- baric tags for relative and absolute quantitation (iTRAQ) proteomic analysis. Methods: A 0.4-µm pore size indirect co- culture system was established with female mice endometrial stromal cells (EStCs) restricted in the upper Transwell chamber and BMSCs in the lower well plate. After indirect co-culture for several days, the BMSCs were revealed to progressively differentiate towards EECs in vitro. Then, four groups were divided according to different co-culture days with single culture groups of BMSCs as controls.
    [Show full text]
  • (HMGB1) Deletion Leads to Small Heart and Glycolipid Metabolic
    Yu et al. Cell Death Discovery (2020) 6:106 https://doi.org/10.1038/s41420-020-00340-9 Cell Death Discovery ARTICLE Open Access Cardiomyocyte-restricted high-mobility group box 1 (HMGB1) deletion leads to small heart and glycolipid metabolic disorder through GR/PGC-1α signalling Peng Yu 1, Ming Liu2,BaoliZhang3,YingYu2,EnyongSu3,ShiyaoXie3,LeiZhang3,XueYang3,HongJiang 3, Ruizhen Chen3, Yunzeng Zou3 and Junbo Ge3 Abstract Cardiac growth and remodelling are key biological processes influencing the physiological performance of the heart, and a previous study showed a critical role for intracellular HMGB1 in vitro. However, the in vivo study, which used conditional Hmgb1 ablation, did not show a significant effect on cellular or organic function. We have demonstrated the extracellular effect of HMGB1 as a pro-inflammatory molecule on cardiac remodelling. In this study, we found that HMGB1 deletion by cTnT-Cre in mouse hearts altered glucocorticoid receptor (GR) function and glycolipid metabolism, eventually leading to growth retardation, small heart and heart failure. The subcellular morphology did not show a significant change caused by HMGB1 knockout. The heart showed significant elevation of glycolysis, free fatty acid deposition and related enzyme changes. Transcriptomic analysis revealed a list of differentially expressed genes that coincide with glucocorticoid receptor function in neonatal mice and a significant increase in inflammatory genes in 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; adult mice. Cardiac HMGB1 knockout led to a series of changes in PGC-1α, UCP3 and GyK, which were the cause of metabolic changes and further impacted cardiac function. Ckmm-Cre Hmgb1fl/fl mice did not show a specific phenotype, which was consistent with the reported negative result of cardiomyocyte-specific Hmgb1 deletion via MHC-Cre.
    [Show full text]
  • (KPNA7), a Divergent Member of the Importin a Family of Nuclear Import
    Kelley et al. BMC Cell Biology 2010, 11:63 http://www.biomedcentral.com/1471-2121/11/63 RESEARCH ARTICLE Open Access Karyopherin a7 (KPNA7), a divergent member of the importin a family of nuclear import receptors Joshua B Kelley1, Ashley M Talley1, Adam Spencer1, Daniel Gioeli2, Bryce M Paschal1,3* Abstract Background: Classical nuclear localization signal (NLS) dependent nuclear import is carried out by a heterodimer of importin a and importin b. NLS cargo is recognized by importin a, which is bound by importin b. Importin b mediates translocation of the complex through the central channel of the nuclear pore, and upon reaching the nucleus, RanGTP binding to importin b triggers disassembly of the complex. To date, six importin a family members, encoded by separate genes, have been described in humans. Results: We sequenced and characterized a seventh member of the importin a family of transport factors, karyopherin a 7 (KPNA7), which is most closely related to KPNA2. The domain of KPNA7 that binds Importin b (IBB) is divergent, and shows stronger binding to importin b than the IBB domains from of other importin a family members. With regard to NLS recognition, KPNA7 binds to the retinoblastoma (RB) NLS to a similar degree as KPNA2, but it fails to bind the SV40-NLS and the human nucleoplasmin (NPM) NLS. KPNA7 shows a predominantly nuclear distribution under steady state conditions, which contrasts with KPNA2 which is primarily cytoplasmic. Conclusion: KPNA7 is a novel importin a family member in humans that belongs to the importin a2 subfamily. KPNA7 shows different subcellular localization and NLS binding characteristics compared to other members of the importin a family.
    [Show full text]
  • Supplementary Table 2
    Supplementary Table 2. Differentially Expressed Genes following Sham treatment relative to Untreated Controls Fold Change Accession Name Symbol 3 h 12 h NM_013121 CD28 antigen Cd28 12.82 BG665360 FMS-like tyrosine kinase 1 Flt1 9.63 NM_012701 Adrenergic receptor, beta 1 Adrb1 8.24 0.46 U20796 Nuclear receptor subfamily 1, group D, member 2 Nr1d2 7.22 NM_017116 Calpain 2 Capn2 6.41 BE097282 Guanine nucleotide binding protein, alpha 12 Gna12 6.21 NM_053328 Basic helix-loop-helix domain containing, class B2 Bhlhb2 5.79 NM_053831 Guanylate cyclase 2f Gucy2f 5.71 AW251703 Tumor necrosis factor receptor superfamily, member 12a Tnfrsf12a 5.57 NM_021691 Twist homolog 2 (Drosophila) Twist2 5.42 NM_133550 Fc receptor, IgE, low affinity II, alpha polypeptide Fcer2a 4.93 NM_031120 Signal sequence receptor, gamma Ssr3 4.84 NM_053544 Secreted frizzled-related protein 4 Sfrp4 4.73 NM_053910 Pleckstrin homology, Sec7 and coiled/coil domains 1 Pscd1 4.69 BE113233 Suppressor of cytokine signaling 2 Socs2 4.68 NM_053949 Potassium voltage-gated channel, subfamily H (eag- Kcnh2 4.60 related), member 2 NM_017305 Glutamate cysteine ligase, modifier subunit Gclm 4.59 NM_017309 Protein phospatase 3, regulatory subunit B, alpha Ppp3r1 4.54 isoform,type 1 NM_012765 5-hydroxytryptamine (serotonin) receptor 2C Htr2c 4.46 NM_017218 V-erb-b2 erythroblastic leukemia viral oncogene homolog Erbb3 4.42 3 (avian) AW918369 Zinc finger protein 191 Zfp191 4.38 NM_031034 Guanine nucleotide binding protein, alpha 12 Gna12 4.38 NM_017020 Interleukin 6 receptor Il6r 4.37 AJ002942
    [Show full text]
  • KPNA2 Promotes Metabolic Reprogramming in Glioblastomas By
    Li et al. Journal of Experimental & Clinical Cancer Research (2018) 37:194 https://doi.org/10.1186/s13046-018-0861-9 RESEARCH Open Access KPNA2 promotes metabolic reprogramming in glioblastomas by regulation of c-myc Jie Li1†, Qian Liu2†, Zihao Liu3, Qian Xia3, Zihao Zhang3, Rui Zhang1, Taihong Gao1, Guangyan Gu2, Yanan Wang2, Dan Wang2, Xiuyang Chen1, Yihang Yang1, Dong He1 and Tao Xin1,4* Abstract Background: Cancer cells maintain energy metabolism mainly by glycolysis, even under sufficient oxygen conditions. It gives cancer cells better growth advantages under complicated internal environment. KPNA2 is a novel oncogene that has received much attention in recent years, but the exact mechanisms of KPNA2 in tumorigenesis and progression are largely unknown. Especially its potential roles in the metabolic transformation of tumors still remain to be explored. Methods: The expressions of KPNA2 in glioblastoma and normal human brain samples were analyzed by immunohistochemical analysis. The activities of key enzymes in glycolysis, the production of lactate acid and glucose uptake were investigated by colorimetry. GLUT-1 expression was measured by flow cytometry. CCK8 was used to examine the cell viability in vitro, and the xenograft models in nude mice were established to explore the roles of KPNA2 in vivo. In addition, Co-IP, subcellular fractionation, western blot, immunofluorescence and luciferase assay were used to investigate the internal connection between KPNA2, c-myc and E2F1. Results: In the present study, we found that KPNA2 was highly expressed in the glioma compared to the normal brain tissues. Level of KPNA2 was an independent predictor of prognosis in the glioma patients.
    [Show full text]
  • Supplemental Table 1
    Symbol Gene name MIN6.EXO MIN6.M1 MIN6.M2 MIN6.M3 MIN6.M4 A2m alpha-2-macroglobulin A2m Acat1 acetyl-Coenzyme A acetyltransferase 1 Acat1 Acly ATP citrate lyase Acly Acly Acly Act Actin Act Act Act Act Aga aspartylglucosaminidase Aga Ahcy S-adenosylhomocysteine hydrolase Ahcy Alb Albumin Alb Alb Alb Aldoa aldolase A, fructose-bisphosphate Aldoa Anxa5 Annexin A5 Anxa5 AP1 Adaptor-related protein complex AP1 AP2 Adaptor protein complex AP2 Arf1 ADP-ribosylation factor 1 Arf1 Atp1a1 ATPase Na/K transpoting Atp1a1 ATP1b1 Na/K ATPase beta subunit ATP1b1 ATP6V1 ATPase, H+ transporting.. ATP6V1 ATP6v1 ATP6v1 Banf1 Barrier to autointegration factor Banf1 Basp1 brain abundant, memrane signal protein 1 Basp1 C3 complement C3 C3 C3 C3 C4 Complement C4 C4 C4 C4 Calm2 calmodulin 2 (phosphorylase kinase, delta) Calm2 Capn5 Calpain 5 Capn5 Capn5 Cct5 chaperonin subunit 5 Cct5 Cct8 chaperonin subunit 8 Cct8 CD147 basigin CD147 CD63 CD63 CD63 CD81 CD81 CD81 CD81 CD81 CD81 CD81 CD82 CD82 CD82 CD82 CD90.2 thy1.2 CD90.2 CD98 Slc3a2 CD98 CD98 Cdc42 Cell division cycle 42 Cdc42 Cfl1 Cofilin 1 Cfl1 Cfl1 Chmp4b chromatin modifying protein 4B Chmp4b Chmp5 chromatin modifying protein 5 Chmp5 Clta clathrin, light polypeptide A Clta Cltc Clathrin Hc Cltc Cltc Cltc Cltc Clu clusterin Clu Col16a1 collagen 16a1 Col16a1 Col2 Collagen type II Col2a1 Col2 Col6 Collagen type VI alpha 3 Col6a3 Col6 CpE carboxypeptidase E CpE CpE CpE, CpH CpE CpE Cspg4 Chondroitin sulfate proteoglycan 4 Cspg4 CyCAP Cyclophilin C-associated protein CyCAP CyCAP Dnpep aspartyl aminopeptidase Dnpep Dstn destrin Dstn EDIL3 EGF-like repeat discoidin.
    [Show full text]
  • Regulation of Protein Kinase Cδ Nuclear Import and Apoptosis by Mechanistic Target of Rapamycin Complex-1 Antonio Layoun1,5, Alexander A
    www.nature.com/scientificreports Corrected: Publisher Correction OPEN Regulation of protein kinase Cδ Nuclear Import and Apoptosis by Mechanistic Target of Rapamycin Complex-1 Antonio Layoun1,5, Alexander A. Goldberg1,5, Ayesha Baig1, Mikaela Eng1, Ortal Attias1, Kristof Nelson1, Alexandra Carella1, Nahomi Amberber1, Jill A. Fielhaber1, Kwang-Bo Joung1, T. Martin Schmeing 2, Yingshan Han1, Jefrey Downey3, Maziar Divangahi3, Philippe P. Roux 4 & Arnold S. Kristof1* Inactivation of the protein complex ‘mechanistic target of rapamycin complex 1’ (mTORC1) can increase the nuclear content of transcriptional regulators of metabolism and apoptosis. Previous studies established that nuclear import of signal transducer and activator of transcription-1 (STAT1) requires the mTORC1-associated adaptor karyopherin-α1 (KPNA1) when mTORC1 activity is reduced. However, the role of other mTORC1-interacting proteins in the complex, including ‘protein kinase C delta’ (PKCδ), have not been well characterized. In this study, we demonstrate that PKCδ, a STAT1 kinase, contains a functional ‘target of rapamycin signaling’ (TOS) motif that directs its interaction with mTORC1. Depletion of KPNA1 by RNAi prevented the nuclear import of PKCδ in cells exposed to the mTORC1 inhibitor rapamycin or amino acid restriction. Mutation of the TOS motif in PKCδ led to its loss of regulation by mTORC1 or karyopherin-α1, resulting in increased constitutive nuclear content. In cells expressing wild-type PKCδ, STAT1 activity and apoptosis were increased by rapamycin or interferon-β. Those expressing the PKCδ TOS mutant exhibited increased STAT1 activity and apoptosis; further enhancement by rapamycin or interferon-β, however, was lost. Therefore, the TOS motif in PKCδ is a novel structural mechanism by which mTORC1 prevents PKCδ and STAT1 nuclear import, and apoptosis.
    [Show full text]
  • Nucleocytoplasmic Transport: Regulatory Mechanisms and the Implications in Neurodegeneration
    International Journal of Molecular Sciences Review Nucleocytoplasmic Transport: Regulatory Mechanisms and the Implications in Neurodegeneration Baojin Ding * and Masood Sepehrimanesh Department of Biology, University of Louisiana at Lafayette, 410 East Saint Mary Boulevard, Lafayette, LA 70503, USA; [email protected] * Correspondence: [email protected] Abstract: Nucleocytoplasmic transport (NCT) across the nuclear envelope is precisely regulated in eukaryotic cells, and it plays critical roles in maintenance of cellular homeostasis. Accumulating evidence has demonstrated that dysregulations of NCT are implicated in aging and age-related neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer’s disease (AD), and Huntington disease (HD). This is an emerging research field. The molecular mechanisms underlying impaired NCT and the pathogenesis leading to neurodegener- ation are not clear. In this review, we comprehensively described the components of NCT machinery, including nuclear envelope (NE), nuclear pore complex (NPC), importins and exportins, RanGTPase and its regulators, and the regulatory mechanisms of nuclear transport of both protein and transcript cargos. Additionally, we discussed the possible molecular mechanisms of impaired NCT underlying aging and neurodegenerative diseases, such as ALS/FTD, HD, and AD. Keywords: Alzheimer’s disease; amyotrophic lateral sclerosis; Huntington disease; neurodegenera- tive diseases; nuclear pore complex; nucleocytoplasmic transport; Ran GTPase Citation: Ding, B.; Sepehrimanesh, M. Nucleocytoplasmic Transport: Regulatory Mechanisms and the Implications in Neurodegeneration. 1. Introduction Int. J. Mol. Sci. 2021, 22, 4165. As a hallmark of eukaryotic cells, the genetic materials are separated from the cyto- https://doi.org/10.3390/ijms plasmic contents by a highly regulated membrane, called nuclear envelope (NE), which 22084165 has two concentric bilayer membranes, the inner nuclear membrane (INM), and outer nuclear membrane (ONM).
    [Show full text]
  • Thesis Was to Elucidate the Function of Recently Discovered Nuclear IGF-1R As Well As to Investigate Its Nuclear Translocation Pathway
    From the Department of Oncology-Pathology Karolinska Institutet, Stockholm, Sweden FROM MEMBRANE TO NUCLEUS: NEW ROLES AND FUNCTIONS OF SUMOYLATED IGF-1R AND EGFR Sylvia Packham Stockholm 2015 All previously published papers were reproduced with permission from the publisher. Published by Karolinska Institutet. Printed by AJ E-print AB, Stockholm, Sweden © Sylvia Packham, 2015 ISBN 978-91-7549-877-5 To my beloved Justin and Family ABSTRACT Cell surface receptor tyrosine kinases (RTKs) role in cell signaling have been studied for decades and their role in cancer progression are undisputable. The insulin-like growth factor 1 receptor, IGF-1R, has been demonstrated to play a critical part in tumorigenesis; downregulation of the IGF-1R in tumor xenografts results in complete tumor regression. Previously, RTK research has focused on the canonical signaling pathways activated by ligand binding at the plasma membrane. However, strong evidence keeps emerging that several RTKs have a second functionally mechanism, inside the cell nucleus, where the receptors reside after ligand stimulation. The aim of this thesis was to elucidate the function of recently discovered nuclear IGF-1R as well as to investigate its nuclear translocation pathway. Since it was previously shown that SUMOylation of the IGF-1R is essential for its nuclear translocation we also set out to investigate SUMO modification of the epidermal growth factor receptor (EGFR). In paper I, we present a functional role for nuclear IGF-1R in gene transcription. Inside the nucleus, IGF-1R functions as a co-activator to LEF-1/TCF transcription factor. Nuclear IGF-1R enhances transcription of cyclin D1 and axin2, and we show that it is enriched in the cyclin D1 promoter region.
    [Show full text]
  • Nuclear Localization Signal-Independent and Importin/Karyopherin-Independent Nuclear Import of B-Catenin François Fagotto*, Ursula Glück and Barry M
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE Researchprovided byPaper Elsevier -181 Publisher Connector Nuclear localization signal-independent and importin/karyopherin-independent nuclear import of b-catenin François Fagotto*, Ursula Glück and Barry M. Gumbiner Background: Control of the nuclear localization of specific proteins is an Address: Cellular Biochemistry and Biophysics important mechanism for regulating many signal transduction pathways. Upon Program, Memorial Sloan–Kettering Cancer Center, 1275 York Avenue, Box 564, New York 10021, activation of the Wnt signaling pathway, β-catenin localizes into the nucleus and USA. interacts with TCF/LEF-1 (T-cell factor/lymphocyte enhancer factor-1) transcription factors, triggering activation of downstream genes. The role of *Present address: Max-Plank Institute for regulated nuclear localization in β-catenin signaling is still unclear. β-catenin has Developmental Biology, Division for Cell Biology, Spemannstrasse 35-V, 72076 Tübingen, Germany. no nuclear localization sequence (NLS). Although it has been reported that β- catenin can piggyback into the nucleus by binding to TCF/LEF-1, there is Correspondence: Barry M. Gumbiner evidence that its import is independent of TCF/LEF-1 in vivo. Therefore, the E-mail: [email protected] mechanism for β-catenin nuclear localization remains to be established. Received: 22 October 1997 15 January 1998 β Revised: Results: We have analyzed -catenin nuclear import in an in vitro assay using Accepted: 15 January 1998 permeabilized cells. β-catenin docks specifically onto the nuclear envelope in the absence of other cytosolic factors. Docking is not inhibited by an NLS Published: 23 January 1998 peptide and does not require importins/karyopherins, the receptors for classical Current Biology 1998, 8:181–190 β β NLS substrates.
    [Show full text]
  • Comparative Gene Expression Analysis to Identify Common Factors in Multiple Cancers
    COMPARATIVE GENE EXPRESSION ANALYSIS TO IDENTIFY COMMON FACTORS IN MULTIPLE CANCERS DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Leszek A. Rybaczyk, B.A. ***** The Ohio State University 2008 Dissertation Committee: Professor Kun Huang, Adviser Professor Jeffery Kuret Approved by Professor Randy Nelson Professor Daniel Janies ------------------------------------------- Adviser Integrated Biomedical Science Graduate Program ABSTRACT Most current cancer research is focused on tissue-specific genetic mutations. Familial inheritance (e.g., APC in colon cancer), genetic mutation (e.g., p53), and overexpression of growth receptors (e.g., Her2-neu in breast cancer) can potentially lead to aberrant replication of a cell. Studies of these changes provide tremendous information about tissue-specific effects but are less informative about common changes that occur in multiple tissues. The similarity in the behavior of cancers from different organ systems and species suggests that a pervasive mechanism drives carcinogenesis, regardless of the specific tissue or species. In order to detect this mechanism, I applied three tiers of analysis at different levels: hypothesis testing on individual pathways to identify significant expression changes within each dataset, intersection of results between different datasets to find common themes across experiments, and Pearson correlations between individual genes to identify correlated genes within each dataset. By comparing a variety of cancers from different tissues and species, I was able to separate tissue and species specific effects from cancer specific effects. I found that downregulation of Monoamine Oxidase A is an indicator of this pervasive mechanism and can potentially be used to detect pathways and functions related to the initiation, promotion, and progression of cancer.
    [Show full text]
  • Transcriptomic Analysis of Patients with Tetralogy of Fallot Reveals the Effect of Chronic Hypoxia on Myocardial Gene Expression
    Ghorbel et al Congenital Heart Disease Transcriptomic analysis of patients with tetralogy of Fallot reveals the effect of chronic hypoxia on myocardial gene expression Mohamed T. Ghorbel, PhD, Myriam Cherif, PhD, Emma Jenkins, PhD, Amir Mokhtari, MRCS, Damien Kenny, MRCPCH, Gianni D. Angelini, FRCS, and Massimo Caputo, MD Objectives: In cyanotic patients undergoing repair of heart defects, chronic hypoxia is thought to lead to greater susceptibility to ischemia and reoxygenation injury. We sought to find an explanation to such a hypothesis by investigating the cardiac gene expression in patients with tetralogy of Fallot undergoing cardiac surgery. CHD Methods: The myocardial gene profile was investigated in right ventricular biopsy specimens obtained from 20 patients with a diagnosis of cyanotic (n ¼ 11) or acyanotic (n ¼ 9) tetralogy of Fallot undergoing surgical repair. Oligonucleotide microarray analyses were performed on the samples, and the array results were validated with Western blotting and enzyme-linked immunosorbent assay. Results: Data revealed 795 differentially expressed genes in cyanotic versus acyanotic hearts, with 198 upregu- lated and 597 downregulated. Growth/morphogenesis, remodeling, and apoptosis emerged as dominant func- tional themes for the upregulated genes and included the apoptotic gene TRAIL (tumor necrosis factor–related apoptosis-inducing ligand), the remodeling factor OPN (osteopontin), and the mitochondrial function gene COX11 (cytochrome-c oxidase 11). In contrast, transcription, mitogen-activated protein kinase signaling, and contractile machinery were the dominant functional classes for the downregulated genes, which included the calcium-handling gene NCX1 (sodium-calcium exchanger). Protein levels of COX11, NCX1, OPN, and LYZ (ly- sozyme) in the myocardium followed the same pattern obtained by means of transcriptomics.
    [Show full text]