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  1. Article ; Online: From bedside to bench: regulation of host factors in SARS-CoV-2 infection.

    Ong, Samantha Y Q / Flyamer, Ilya M / Bickmore, Wendy A / Biddie, Simon C

    Experimental & molecular medicine

    2021  Volume 53, Issue 4, Page(s) 483–494

    Abstract: The zoonotic coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2), which causes COVID-19 (coronavirus disease-2019), has resulted in a pandemic. This has led to an urgent need to understand the molecular determinants of SARS-CoV-2 ... ...

    Abstract The zoonotic coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2), which causes COVID-19 (coronavirus disease-2019), has resulted in a pandemic. This has led to an urgent need to understand the molecular determinants of SARS-CoV-2 infection, factors associated with COVID-19 heterogeneity and severity, and therapeutic options for these patients. In this review, we discuss the role of host factors in SARS-CoV-2 infection and describe variations in host factor expression as mechanisms underlying the symptoms and severity of COVID-19. We focus on two host factors, angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), implicated in SARS-CoV-2 infection. We also discuss genetic variants associated with COVID-19 severity revealed in selected patients and based on genome-wide association studies (GWASs). Furthermore, we highlight important advances in cell and chromatin biology, such as single-cell RNA and chromatin sequencing and chromosomal conformation assays, as methods that may aid in the discovery of viral-host interactions in COVID-19. Understanding how regulation of host factor genes varies in physiological and pathological states might explain the heterogeneity observed in SARS-CoV-2 infection, help identify pathways for therapeutic development, and identify patients most likely to progress to severe COVID-19.
    MeSH term(s) Angiotensin-Converting Enzyme 2/genetics ; Angiotensin-Converting Enzyme 2/metabolism ; COVID-19/etiology ; COVID-19/genetics ; Gene Expression ; Genetic Variation ; Host-Pathogen Interactions/physiology ; Humans ; Interferon Type I/genetics ; Interferon Type I/metabolism ; Lung/pathology ; Lung/virology ; Serine Endopeptidases/genetics ; Serine Endopeptidases/metabolism
    Chemical Substances Interferon Type I ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Serine Endopeptidases (EC 3.4.21.-) ; TMPRSS2 protein, human (EC 3.4.21.-)
    Language English
    Publishing date 2021-04-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1328915-9
    ISSN 2092-6413 ; 1226-3613 ; 0378-8512
    ISSN (online) 2092-6413
    ISSN 1226-3613 ; 0378-8512
    DOI 10.1038/s12276-021-00595-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 4775: Show issues Location:
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  2. Article ; Online: Salmonella Effector SteE Converts the Mammalian Serine/Threonine Kinase GSK3 into a Tyrosine Kinase to Direct Macrophage Polarization.

    Panagi, Ioanna / Jennings, Elliott / Zeng, Jingkun / Günster, Regina A / Stones, Cullum D / Mak, Hazel / Jin, Enkai / Stapels, Daphne A C / Subari, Nur Z / Pham, Trung H M / Brewer, Susan M / Ong, Samantha Y Q / Monack, Denise M / Helaine, Sophie / Thurston, Teresa L M

    Cell host & microbe

    2019  Volume 27, Issue 1, Page(s) 41–53.e6

    Abstract: Many Gram-negative bacterial pathogens antagonize anti-bacterial immunity through translocated effector proteins that inhibit pro-inflammatory signaling. In addition, the intracellular pathogen Salmonella enterica serovar Typhimurium initiates an anti- ... ...

    Abstract Many Gram-negative bacterial pathogens antagonize anti-bacterial immunity through translocated effector proteins that inhibit pro-inflammatory signaling. In addition, the intracellular pathogen Salmonella enterica serovar Typhimurium initiates an anti-inflammatory transcriptional response in macrophages through its effector protein SteE. However, the target(s) and molecular mechanism of SteE remain unknown. Here, we demonstrate that SteE converts both the amino acid and substrate specificity of the host pleiotropic serine/threonine kinase GSK3. SteE itself is a substrate of GSK3, and phosphorylation of SteE is required for its activity. Remarkably, phosphorylated SteE then forces GSK3 to phosphorylate the non-canonical substrate signal transducer and activator of transcription 3 (STAT3) on tyrosine-705. This results in STAT3 activation, which along with GSK3 is required for SteE-mediated upregulation of the anti-inflammatory M2 macrophage marker interleukin-4Rα (IL-4Rα). Overall, the conversion of GSK3 to a tyrosine-directed kinase represents a tightly regulated event that enables a bacterial virulence protein to reprogram innate immune signaling and establish an anti-inflammatory environment.
    MeSH term(s) Animals ; Bacterial Proteins/metabolism ; Glycogen Synthase Kinase 3/metabolism ; HEK293 Cells ; HeLa Cells ; Host Microbial Interactions/immunology ; Humans ; Interleukin-4/metabolism ; Macrophage Activation ; Macrophages/metabolism ; Macrophages/microbiology ; Mice ; Mice, Inbred C57BL ; Protein Serine-Threonine Kinases/metabolism ; Protein-Tyrosine Kinases/metabolism ; STAT3 Transcription Factor/metabolism ; Salmonella typhimurium/immunology ; Salmonella typhimurium/metabolism ; Salmonella typhimurium/pathogenicity ; Virulence/immunology
    Chemical Substances Bacterial Proteins ; STAT3 Transcription Factor ; STAT3 protein, human ; Interleukin-4 (207137-56-2) ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; Glycogen Synthase Kinase 3 (EC 2.7.11.26)
    Language English
    Publishing date 2019-12-17
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2278004-X
    ISSN 1934-6069 ; 1931-3128
    ISSN (online) 1934-6069
    ISSN 1931-3128
    DOI 10.1016/j.chom.2019.11.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

    Phelan, Catherine M / Kuchenbaecker, Karoline B / Tyrer, Jonathan P / Kar, Siddhartha P / Lawrenson, Kate / Winham, Stacey J / Dennis, Joe / Pirie, Ailith / Riggan, Marjorie J / Chornokur, Ganna / Earp, Madalene A / Lyra, Paulo C / Lee, Janet M / Coetzee, Simon / Beesley, Jonathan / McGuffog, Lesley / Soucy, Penny / Dicks, Ed / Lee, Andrew /
    Barrowdale, Daniel / Lecarpentier, Julie / Leslie, Goska / Aalfs, Cora M / Aben, Katja K H / Adams, Marcia / Adlard, Julian / Andrulis, Irene L / Anton-Culver, Hoda / Antonenkova, Natalia / Aravantinos, Gerasimos / Arnold, Norbert / Arun, Banu K / Arver, Brita / Azzollini, Jacopo / Balmaña, Judith / Banerjee, Susana N / Barjhoux, Laure / Barkardottir, Rosa B / Bean, Yukie / Beckmann, Matthias W / Beeghly-Fadiel, Alicia / Benitez, Javier / Bermisheva, Marina / Bernardini, Marcus Q / Birrer, Michael J / Bjorge, Line / Black, Amanda / Blankstein, Kenneth / Blok, Marinus J / Bodelon, Clara / Bogdanova, Natalia / Bojesen, Anders / Bonanni, Bernardo / Borg, Åke / Bradbury, Angela R / Brenton, James D / Brewer, Carole / Brinton, Louise / Broberg, Per / Brooks-Wilson, Angela / Bruinsma, Fiona / Brunet, Joan / Buecher, Bruno / Butzow, Ralf / Buys, Saundra S / Caldes, Trinidad / Caligo, Maria A / Campbell, Ian / Cannioto, Rikki / Carney, Michael E / Cescon, Terence / Chan, Salina B / Chang-Claude, Jenny / Chanock, Stephen / Chen, Xiao Qing / Chiew, Yoke-Eng / Chiquette, Jocelyne / Chung, Wendy K / Claes, Kathleen B M / Conner, Thomas / Cook, Linda S / Cook, Jackie / Cramer, Daniel W / Cunningham, Julie M / D'Aloisio, Aimee A / Daly, Mary B / Damiola, Francesca / Damirovna, Sakaeva Dina / Dansonka-Mieszkowska, Agnieszka / Dao, Fanny / Davidson, Rosemarie / DeFazio, Anna / Delnatte, Capucine / Doheny, Kimberly F / Diez, Orland / Ding, Yuan Chun / Doherty, Jennifer Anne / Domchek, Susan M / Dorfling, Cecilia M / Dörk, Thilo / Dossus, Laure / Duran, Mercedes / Dürst, Matthias / Dworniczak, Bernd / Eccles, Diana / Edwards, Todd / Eeles, Ros / Eilber, Ursula / Ejlertsen, Bent / Ekici, Arif B / Ellis, Steve / Elvira, Mingajeva / Eng, Kevin H / Engel, Christoph / Evans, D Gareth / Fasching, Peter A / Ferguson, Sarah / Ferrer, Sandra Fert / Flanagan, James M / Fogarty, Zachary C / Fortner, Renée T / Fostira, Florentia / Foulkes, William D / Fountzilas, George / Fridley, Brooke L / Friebel, Tara M / Friedman, Eitan / Frost, Debra / Ganz, Patricia A / Garber, Judy / García, María J / Garcia-Barberan, Vanesa / Gehrig, Andrea / Gentry-Maharaj, Aleksandra / Gerdes, Anne-Marie / Giles, Graham G / Glasspool, Rosalind / Glendon, Gord / Godwin, Andrew K / Goldgar, David E / Goranova, Teodora / Gore, Martin / Greene, Mark H / Gronwald, Jacek / Gruber, Stephen / Hahnen, Eric / Haiman, Christopher A / Håkansson, Niclas / Hamann, Ute / Hansen, Thomas V O / Harrington, Patricia A / Harris, Holly R / Hauke, Jan / Hein, Alexander / Henderson, Alex / Hildebrandt, Michelle A T / Hillemanns, Peter / Hodgson, Shirley / Høgdall, Claus K / Høgdall, Estrid / Hogervorst, Frans B L / Holland, Helene / Hooning, Maartje J / Hosking, Karen / Huang, Ruea-Yea / Hulick, Peter J / Hung, Jillian / Hunter, David J / Huntsman, David G / Huzarski, Tomasz / Imyanitov, Evgeny N / Isaacs, Claudine / Iversen, Edwin S / Izatt, Louise / Izquierdo, Angel / Jakubowska, Anna / James, Paul / Janavicius, Ramunas / Jernetz, Mats / Jensen, Allan / Jensen, Uffe Birk / John, Esther M / Johnatty, Sharon / Jones, Michael E / Kannisto, Päivi / Karlan, Beth Y / Karnezis, Anthony / Kast, Karin / Kennedy, Catherine J / Khusnutdinova, Elza / Kiemeney, Lambertus A / Kiiski, Johanna I / Kim, Sung-Won / Kjaer, Susanne K / Köbel, Martin / Kopperud, Reidun K / Kruse, Torben A / Kupryjanczyk, Jolanta / Kwong, Ava / Laitman, Yael / Lambrechts, Diether / Larrañaga, Nerea / Larson, Melissa C / Lazaro, Conxi / Le, Nhu D / Le Marchand, Loic / Lee, Jong Won / Lele, Shashikant B / Leminen, Arto / Leroux, Dominique / Lester, Jenny / Lesueur, Fabienne / Levine, Douglas A / Liang, Dong / Liebrich, Clemens / Lilyquist, Jenna / Lipworth, Loren / Lissowska, Jolanta / Lu, Karen H / Lubinński, Jan / Luccarini, Craig / Lundvall, Lene / Mai, Phuong L / Mendoza-Fandiño, Gustavo / Manoukian, Siranoush / Massuger, Leon F A G / May, Taymaa / Mazoyer, Sylvie / McAlpine, Jessica N / McGuire, Valerie / McLaughlin, John R / McNeish, Iain / Meijers-Heijboer, Hanne / Meindl, Alfons / Menon, Usha / Mensenkamp, Arjen R / Merritt, Melissa A / Milne, Roger L / Mitchell, Gillian / Modugno, Francesmary / Moes-Sosnowska, Joanna / Moffitt, Melissa / Montagna, Marco / Moysich, Kirsten B / Mulligan, Anna Marie / Musinsky, Jacob / Nathanson, Katherine L / Nedergaard, Lotte / Ness, Roberta B / Neuhausen, Susan L / Nevanlinna, Heli / Niederacher, Dieter / Nussbaum, Robert L / Odunsi, Kunle / Olah, Edith / Olopade, Olufunmilayo I / Olsson, Håkan / Olswold, Curtis / O'Malley, David M / Ong, Kai-Ren / Onland-Moret, N Charlotte / Orr, Nicholas / Orsulic, Sandra / Osorio, Ana / Palli, Domenico / Papi, Laura / Park-Simon, Tjoung-Won / Paul, James / Pearce, Celeste L / Pedersen, Inge Søkilde / Peeters, Petra H M / Peissel, Bernard / Peixoto, Ana / Pejovic, Tanja / Pelttari, Liisa M / Permuth, Jennifer B / Peterlongo, Paolo / Pezzani, Lidia / Pfeiler, Georg / Phillips, Kelly-Anne / Piedmonte, Marion / Pike, Malcolm C / Piskorz, Anna M / Poblete, Samantha R / Pocza, Timea / Poole, Elizabeth M / Poppe, Bruce / Porteous, Mary E / Prieur, Fabienne / Prokofyeva, Darya / Pugh, Elizabeth / Pujana, Miquel Angel / Pujol, Pascal / Radice, Paolo / Rantala, Johanna / Rappaport-Fuerhauser, Christine / Rennert, Gad / Rhiem, Kerstin / Rice, Patricia / Richardson, Andrea / Robson, Mark / Rodriguez, Gustavo C / Rodríguez-Antona, Cristina / Romm, Jane / Rookus, Matti A / Rossing, Mary Anne / Rothstein, Joseph H / Rudolph, Anja / Runnebaum, Ingo B / Salvesen, Helga B / Sandler, Dale P / Schoemaker, Minouk J / Senter, Leigha / Setiawan, V Wendy / Severi, Gianluca / Sharma, Priyanka / Shelford, Tameka / Siddiqui, Nadeem / Side, Lucy E / Sieh, Weiva / Singer, Christian F / Sobol, Hagay / Song, Honglin / Southey, Melissa C / Spurdle, Amanda B / Stadler, Zsofia / Steinemann, Doris / Stoppa-Lyonnet, Dominique / Sucheston-Campbell, Lara E / Sukiennicki, Grzegorz / Sutphen, Rebecca / Sutter, Christian / Swerdlow, Anthony J / Szabo, Csilla I / Szafron, Lukasz / Tan, Yen Y / Taylor, Jack A / Tea, Muy-Kheng / Teixeira, Manuel R / Teo, Soo-Hwang / Terry, Kathryn L / Thompson, Pamela J / Thomsen, Liv Cecilie Vestrheim / Thull, Darcy L / Tihomirova, Laima / Tinker, Anna V / Tischkowitz, Marc / Tognazzo, Silvia / Toland, Amanda Ewart / Tone, Alicia / Trabert, Britton / Travis, Ruth C / Trichopoulou, Antonia / Tung, Nadine / Tworoger, Shelley S / van Altena, Anne M / Van Den Berg, David / van der Hout, Annemarie H / van der Luijt, Rob B / Van Heetvelde, Mattias / Van Nieuwenhuysen, Els / van Rensburg, Elizabeth J / Vanderstichele, Adriaan / Varon-Mateeva, Raymonda / Vega, Ana / Edwards, Digna Velez / Vergote, Ignace / Vierkant, Robert A / Vijai, Joseph / Vratimos, Athanassios / Walker, Lisa / Walsh, Christine / Wand, Dorothea / Wang-Gohrke, Shan / Wappenschmidt, Barbara / Webb, Penelope M / Weinberg, Clarice R / Weitzel, Jeffrey N / Wentzensen, Nicolas / Whittemore, Alice S / Wijnen, Juul T / Wilkens, Lynne R / Wolk, Alicja / Woo, Michelle / Wu, Xifeng / Wu, Anna H / Yang, Hannah / Yannoukakos, Drakoulis / Ziogas, Argyrios / Zorn, Kristin K / Narod, Steven A / Easton, Douglas F / Amos, Christopher I / Schildkraut, Joellen M / Ramus, Susan J / Ottini, Laura / Goodman, Marc T / Park, Sue K / Kelemen, Linda E / Risch, Harvey A / Thomassen, Mads / Offit, Kenneth / Simard, Jacques / Schmutzler, Rita Katharina / Hazelett, Dennis / Monteiro, Alvaro N / Couch, Fergus J / Berchuck, Andrew / Chenevix-Trench, Georgia / Goode, Ellen L / Sellers, Thomas A / Gayther, Simon A / Antoniou, Antonis C / Pharoah, Paul D P

    Nature genetics

    2017  Volume 49, Issue 5, Page(s) 680–691

    Abstract: To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for ...

    Abstract To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.
    MeSH term(s) Alleles ; BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; Carcinoma, Ovarian Epithelial ; Female ; Genetic Loci/genetics ; Genetic Predisposition to Disease/genetics ; Genome-Wide Association Study ; Genotype ; Humans ; Meta-Analysis as Topic ; Mutation ; Neoplasms, Glandular and Epithelial/genetics ; Neoplasms, Glandular and Epithelial/pathology ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; Polymorphism, Single Nucleotide ; Risk Factors ; Telomere-Binding Proteins/genetics
    Chemical Substances BRCA1 Protein ; BRCA1 protein, human ; BRCA2 Protein ; BRCA2 protein, human ; Stn1 protein, human ; Telomere-Binding Proteins
    Language English
    Publishing date 2017-03-27
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1108734-1
    ISSN 1546-1718 ; 1061-4036
    ISSN (online) 1546-1718
    ISSN 1061-4036
    DOI 10.1038/ng.3826
    Database MEDical Literature Analysis and Retrieval System OnLINE

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