title: Covalent modification of human homeodomain interacting protein kinase 2 by SUMO-1 at lysine 25 affects its stability.
abstract: The HIPK2 protein is a critical regulator of apoptosis and functionally interacts with p53 to increase gene expression. Here we show that human HIPK2 is modified by sumoylation at lysine 25, as revealed by in vivo and in vitro experiments. While SUMO-1 modification of HIPK2 has no influence on its ability to phosphorylate p53 at serine 46, to induce gene expression, and to mediate apoptosis, a non-sumoylatable HIPK2 mutant displays a strongly increased protein stability. The N-terminal SUMO-1 modification site is conserved between all vertebrate HIPK2 proteins and is found in all members of the HIPK family of protein kinases. Accordingly, also human HIPK3 is modified by sumoylation.
authors.affiliation: University of Bern, Department of Chemistry and Biochemistry, Freiestr. 3, CH-3012 Bern, Switzerland.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Gresko
authors.forename: Andreas
authors.initials: A
authors.lastname: Möller
authors.forename: Ana
authors.initials: A
authors.lastname: Roscic
authors.forename: M Lienhard
authors.initials: ML
authors.lastname: Schmitz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004795:Enzyme Stability; D006801:Humans; D008239:Lysine / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D025842:SUMO-1 Protein; D016159:Tumor Suppressor Protein p53; C115114:HIPK2 protein, human; D017346:Protein Serine-Threonine Kinases; D008239:Lysine