Interferon-induced antiviral Mx1 GTPase is associated with components of the SUMO-1 system and promyelocytic leukemia protein nuclear bodies.
Mx proteins are interferon-induced large GTPases, some of which have antiviral activity against a variety of viruses. The murine Mx1 protein accumulates in the nucleus of interferon-treated cells and is active against members of the Orthomyxoviridae family, such as the influenza viruses and Thogoto virus. The mechanism by which Mx1 exerts its antiviral action is still unclear, but an involvement of undefined nuclear factors has been postulated. Using the yeast two-hybrid system, we identified cellular proteins that interact with Mx1 protein. The Mx1 interactors were mainly nuclear proteins. They included Sp100, Daxx, and Bloom's syndrome protein (BLM), all of which are known to localize to specific subnuclear domains called promyelocytic leukemia protein nuclear bodies (PML NBs). In addition, components of the SUMO-1 protein modification system were identified as Mx1-interacting proteins, namely the small ubiquitin-like modifier SUMO-1 and SAE2, which represents subunit 2 of the SUMO-1 activating enzyme. Analysis of the subcellular localization of Mx1 and some of these interacting proteins by confocal microscopy revealed a close spatial association of Mx1 with PML NBs. This suggests a role of PML NBs and SUMO-1 in the antiviral action of Mx1 and may allow us to discover novel functions of this large GTPase.
Engelhardt
O G
OG
Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Freiburg, D-79008, Germany. oengel@ukl.uni-freiburg.de
Ullrich
E
E
Kochs
G
G
Haller
O
O
D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D034961:Antigens, Nuclear; D001324:Autoantigens / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002451:Cell Compartmentation / Q000187:drug effects / Q000235:genetics; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology* / Q000821:virology; D056970:Co-Repressor Proteins; D004265:DNA Helicases / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000187:drug effects / Q000378:metabolism*; D019204:GTP-Binding Proteins; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics; D006367:HeLa Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007150:Immunohistochemistry; D007372:Interferons / Q000378:metabolism* / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D018832:Molecular Chaperones; D064547:Myxovirus Resistance Proteins; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D011506:Proteins / Q000187:drug effects / Q000378:metabolism*; D053484:RecQ Helicases; D025842:SUMO-1 Protein / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D025521:Tumor Suppressor Proteins; D020798:Two-Hybrid System Techniques; D014780:Viruses / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D034961:Antigens, Nuclear; D001324:Autoantigens; D002352:Carrier Proteins; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; C491473:Daxx protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; C579070:Mx1 protein, mouse; D064547:Myxovirus Resistance Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D011506:Proteins; D025842:SUMO-1 Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C066642:SP100 protein, human; C070576:PML protein, human; D007372:Interferons; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D004265:DNA Helicases; D053484:RecQ Helicases