PMID- 10535925 OWN - NLM STAT- MEDLINE DCOM- 19991210 LR - 20211203 IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 96 IP - 22 DP - 1999 Oct 26 TI - Covalent modification of the homeodomain-interacting protein kinase 2 (HIPK2) by the ubiquitin-like protein SUMO-1. PG - 12350-5 AB - 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). FAU - Kim, Y H AU - Kim YH AD - Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. FAU - Choi, C Y AU - Choi CY FAU - Kim, Y AU - Kim Y LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Carrier Proteins) RN - 0 (DNA Primers) RN - 0 (SUMO-1 Protein) RN - 0 (Ubiquitins) RN - EC 2.3.2.23 (Ubiquitin-Conjugating Enzymes) RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.1.- (HIPK2 protein, human) RN - EC 2.7.1.- (Hipk2 protein, mouse) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 6.- (Ligases) RN - EC 6.3.2.- (ubiquitin-conjugating enzyme UBC9) SB - IM MH - Amino Acid Sequence MH - Animals MH - Base Sequence MH - Carrier Proteins/chemistry/*metabolism MH - Cell Line MH - DNA Primers MH - Humans MH - Immunohistochemistry MH - Ligases/metabolism MH - Mice MH - Molecular Sequence Data MH - Protein Kinases/chemistry/*metabolism MH - *Protein Serine-Threonine Kinases MH - SUMO-1 Protein MH - Sequence Homology, Amino Acid MH - *Ubiquitin-Conjugating Enzymes MH - Ubiquitins/*metabolism PMC - PMC22920 EDAT- 1999/10/27 00:00 MHDA- 1999/10/27 00:01 CRDT- 1999/10/27 00:00 PHST- 1999/10/27 00:00 [pubmed] PHST- 1999/10/27 00:01 [medline] PHST- 1999/10/27 00:00 [entrez] AID - 10.1073/pnas.96.22.12350 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12350-5. doi: 10.1073/pnas.96.22.12350.