Covalent modification of human homeodomain interacting protein kinase 2 by SUMO-1 at lysine 25 affects its stability.
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.
Gresko
Ekaterina
E
University of Bern, Department of Chemistry and Biochemistry, Freiestr. 3, CH-3012 Bern, Switzerland.
Möller
Andreas
A
Roscic
Ana
A
Schmitz
M Lienhard
ML
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
D002352:Carrier Proteins; D025842:SUMO-1 Protein; D016159:Tumor Suppressor Protein p53; C115114:HIPK2 protein, human; D017346:Protein Serine-Threonine Kinases; D008239:Lysine