Covalent modification of the homeodomain-interacting protein kinase 2 (HIPK2) by the ubiquitin-like protein SUMO-1.
Posttranslational modifications such as ubiquitination and phosphorylation play an important role in the regulation of cellular protein function. Homeodomain-interacting protein kinase 2 (HIPK2) is a member of the recently identified family of nuclear protein kinases that act as corepressors for homeodomain transcription factors. Here, we show that HIPK2 is regulated by a ubiquitin-like protein, SUMO-1. We demonstrate that HIPK2 localizes to nuclear speckles (dots) by means of a speckle-retention signal. This speckle-retention signal contains a domain that interacts with a mouse ubiquitin-like protein conjugating (E2) enzyme, mUBC9. In cultured cells, HIPK2 is covalently modified by SUMO-1, and the SUMO-1 modification of HIPK2 correlates with its localization to nuclear speckles (dots). Thus, our results provide firm evidence that the nuclear protein kinase HIPK2 can be covalently modified by SUMO-1, which directs its localization to nuclear speckles (dots).
Kim
Y H
YH
Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Choi
C Y
CY
Kim
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D017931:DNA Primers; D006801:Humans; D007150:Immunohistochemistry; D008025:Ligases / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D025842:SUMO-1 Protein; D017386:Sequence Homology, Amino Acid; D044763:Ubiquitin-Conjugating Enzymes; D014452:Ubiquitins / Q000378:metabolism*; D000098843:Ubiquitin-Conjugating Enzyme UBC9
D002352:Carrier Proteins; D017931:DNA Primers; D025842:SUMO-1 Protein; D014452:Ubiquitins; D044763:Ubiquitin-Conjugating Enzymes; D011494:Protein Kinases; C115114:HIPK2 protein, human; C492003:Hipk2 protein, mouse; D017346:Protein Serine-Threonine Kinases; D008025:Ligases; D000098843:Ubiquitin-Conjugating Enzyme UBC9