title: The homeodomain-interacting kinase PKM (HIPK-2) modifies ND10 through both its kinase domain and a SUMO-1 interaction motif and alters the posttranslational modification of PML.
abstract: Homeodomain-interacting protein kinases (HIPK-1, -2, and -3) are a family of enzymes that have been implicated in the phosphorylation and repression of homeodomain-containing transcription factors. HIPK-2 has been found to interact with the SUMO-1-conjugating enzyme Ubc9 and can be covalently modified by SUMO-1. It has also been shown to interact with and phosphorylate p53 and to form punctate speckles in the nucleus of which a proportion colocalize with PML nuclear bodies (ND10). We have previously shown that the hamster equivalent of HIPK-2 (named PKM) interacts with the interferon-induced antiviral GTPase Mx1 and associates with ND10 in interferon-treated cells. Given the connections between the interferon response pathway, constituents of ND10, and SUMO-1-conjugated proteins, we have studied the effects of exogenously expressed PKM on endogenous ND10 proteins. We found that PKM induces structural changes in ND10 that can be attributed both to its kinase activity and to the presence of a functional SUMO-1 interaction motif in the C-terminal half of the protein. The changes in the localization of PML, Sp100, and hDaxx induced by exogenous PKM or fragments thereof correlate with changes in the posttranslationally modified species of PML. We propose that PKM is able to modify ND10 structure by inducing changes in the posttranslational modification of PML and by interacting with SUMO-1 modification pathways.
authors.affiliation: Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, Hermann-Herder-Strasse 11, D-79104 Freiburg, Germany.
authors.forename: Othmar G
authors.initials: OG
authors.lastname: Engelhardt
authors.forename: Chris
authors.initials: C
authors.lastname: Boutell
authors.forename: Anne
authors.initials: A
authors.lastname: Orr
authors.forename: Evelyn
authors.initials: E
authors.lastname: Ullrich
authors.forename: Otto
authors.initials: O
authors.lastname: Haller
authors.forename: Roger D
authors.initials: RD
authors.lastname: Everett
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D022003:Cell Nucleus Structures / Q000201:enzymology* / Q000235:genetics; D002478:Cells, Cultured; D056970:Co-Repressor Proteins; D005057:Eukaryotic Cells / Q000166:cytology / Q000201:enzymology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015473:Leukemia, Promyelocytic, Acute / Q000201:enzymology / Q000235:genetics; D018613:Microscopy, Confocal; D018832:Molecular Chaperones; D009154:Mutation / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D000071156:Promyelocytic Leukemia Protein; D011485:Protein Binding / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D034961:Antigens, Nuclear; D001324:Autoantigens; D002352:Carrier Proteins; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D025842:SUMO-1 Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C066642:SP100 protein, human; C070576:PML protein, human; C115114:HIPK2 protein, human; D017346:Protein Serine-Threonine Kinases