Homeodomain Interacting Protein Kinase 2 (HIPK2)

SPN	R320
HGNC	14402
MGI	1314872
PubMed	17666529
RGD	1309349
UniProt	Q9H2X6
Wiki	HIPK2

HIPK2 is a conserved serine/threonine nuclear kinase that interacts with homeodomain transcription factors.Hipk2 mRNA expression is detectable in day-15 mouse embryos and is strong in day-17 mouse embryos. The predicted 1,198-amino acid HIPK2 protein is 96% identical to the mouse protein and has a CD95-binding site between residues 754 and 899. Northern and dot blot analyses revealed weak but ubiquitous expression of an 11.0-kb transcript that was strongest in neuronal tissue. A 7.8-kb transcript was also detected in uterus, and a strong 1.4-kb transcript was found in pancreas. Confocal microscopy demonstrated a nuclear dot localization even with a C-terminal deletion or a kinase-defective mutant. HIPK2 expressed in cells did not directly associate with CD95 or TNFR1, but did associate with TRADD

Reference

"Isolation and characterization of cDNAs for the protein kinase HIPK2."
Biochim. Biophys. Acta 1518:168-172(2001) [PubMed] [Europe PMC] [Abstract]

"The DNA sequence of human chromosome 7."
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]

"The serine/threonine kinase HIPK2 interacts with TRADD, but not with CD95 or TNF-R1 in 293T cells."
Biochem. Biophys. Res. Commun. 277:513-517(2000) [PubMed] [Europe PMC] [Abstract]

"The homeodomain-interacting protein kinase 2 gene is expressed late in embryogenesis and preferentially in retina, muscle, and neural tissues."
Biochem. Biophys. Res. Commun. 290:942-947(2002) [PubMed] [Europe PMC] [Abstract]

"HIPK2 associates with RanBPM."
Biochem. Biophys. Res. Commun. 297:148-153(2002) [PubMed] [Europe PMC] [Abstract]

"Identification and characterization of HIPK2 interacting with p73 and modulating functions of the p53 family in vivo."
J. Biol. Chem. 277:32020-32028(2002) [PubMed] [Europe PMC] [Abstract]

"Regulation of p53 activity by its interaction with homeodomain-interacting protein kinase-2."
Nat. Cell Biol. 4:1-10(2002) [PubMed] [Europe PMC] [Abstract]

"PML is required for homeodomain-interacting protein kinase 2 (HIPK2)-mediated p53 phosphorylation and cell cycle arrest but is dispensable for the formation of HIPK domains."
Cancer Res. 63:4310-4314(2003) [PubMed] [Europe PMC] [Abstract]

"HIPK2 regulates transforming growth factor-beta-induced c-Jun NH(2)-terminal kinase activation and apoptosis in human hepatoma cells."
Cancer Res. 63:8271-8277(2003) [PubMed] [Europe PMC] [Abstract]

"TP53INP1s and homeodomain-interacting protein kinase-2 (HIPK2) are partners in regulating p53 activity."
J. Biol. Chem. 278:37722-37729(2003) [PubMed] [Europe PMC] [Abstract]

"Requirement of the co-repressor homeodomain-interacting protein kinase 2 for ski-mediated inhibition of bone morphogenetic protein-induced transcriptional activation."
J. Biol. Chem. 278:38998-39005(2003) [PubMed] [Europe PMC] [Abstract]

"Sp100 is important for the stimulatory effect of homeodomain-interacting protein kinase-2 on p53-dependent gene expression."
Oncogene 22:8731-8737(2003) [PubMed] [Europe PMC] [Abstract]

"Desumoylation of homeodomain-interacting protein kinase 2 (HIPK2) through the cytoplasmic-nuclear shuttling of the SUMO-specific protease SENP1."
FEBS Lett. 579:6272-6278(2005) [PubMed] [Europe PMC] [Abstract]

"Autoregulatory control of the p53 response by caspase-mediated processing of HIPK2."
EMBO J. 25:1883-1894(2006) [PubMed] [Europe PMC] [Abstract]

"Phosphorylation-dependent control of Pc2 SUMO E3 ligase activity by its substrate protein HIPK2."
Mol. Cell 24:77-89(2006) [PubMed] [Europe PMC] [Abstract]

"Homeodomain-interacting protein kinase-2 (HIPK2) phosphorylates HMGA1a at Ser-35, Thr-52, and Thr-77 and modulates its DNA binding affinity."
J. Proteome Res. 6:4711-4719(2007) [PubMed] [Europe PMC] [Abstract]

"PEBP2-beta/CBF-beta-dependent phosphorylation of RUNX1 and p300 by HIPK2: implications for leukemogenesis."
Blood 112:3777-3787(2008) [PubMed] [Europe PMC] [Abstract]

"Ubiquitination and degradation of homeodomain-interacting protein kinase 2 by WD40 repeat/SOCS box protein WSB-1."
J. Biol. Chem. 283:4682-4689(2008) [PubMed] [Europe PMC] [Abstract]

"PML activates transcription by protecting HIPK2 and p300 from SCFFbx3-mediated degradation."
Mol. Cell. Biol. 28:7126-7138(2008) [PubMed] [Europe PMC] [Abstract]

"Control of HIPK2 stability by ubiquitin ligase Siah-1 and checkpoint kinases ATM and ATR."
Nat. Cell Biol. 10:812-824(2008) [PubMed] [Europe PMC] [Abstract]

"Transcriptional regulation of hypoxia-inducible factor 1alpha by HIPK2 suggests a novel mechanism to restrain tumor growth."
Biochim. Biophys. Acta 1793:368-377(2009) [PubMed] [Europe PMC] [Abstract]

"Large-scale proteomics analysis of the human kinome."
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]

"PML tumor suppressor is regulated by HIPK2-mediated phosphorylation in response to DNA damage."
Oncogene 28:698-708(2009) [PubMed] [Europe PMC] [Abstract]

"The human protein kinase HIPK2 phosphorylates and downregulates the methyl-binding transcription factor ZBTB4."
Oncogene 28:2535-2544(2009) [PubMed] [Europe PMC] [Abstract]

"Targeting hypoxia in cancer cells by restoring homeodomain interacting protein-kinase 2 and p53 activity and suppressing HIF-1alpha."
PLoS ONE 4:E6819-E6819(2009) [PubMed] [Europe PMC] [Abstract]

"Pancreatic and duodenal homeobox 1 (PDX1) phosphorylation at serine-269 is HIPK2-dependent and affects PDX1 subnuclear localization."
Biochem. Biophys. Res. Commun. 399:155-161(2010) [PubMed] [Europe PMC] [Abstract]

"Homeodomain-interacting protein kinase 2 (HIPK2) targets beta-catenin for phosphorylation and proteasomal degradation."
Biochem. Biophys. Res. Commun. 394:966-971(2010) [PubMed] [Europe PMC] [Abstract]

"Transcriptional regulation of ferritin and antioxidant genes by HIPK2 under genotoxic stress."
J. Cell Sci. 123:3863-3871(2010) [PubMed] [Europe PMC] [Abstract]

"Regulation of genotoxic stress response by homeodomain-interacting protein kinase 2 through phosphorylation of cyclic AMP response element-binding protein at serine 271."
Mol. Biol. Cell 21:2966-2974(2010) [PubMed] [Europe PMC] [Abstract]

"Control of nuclear HIPK2 localization and function by a SUMO interaction motif."
Biochim. Biophys. Acta 1813:283-297(2011) [PubMed] [Europe PMC] [Abstract]

"Role of the SUMO-interacting motif in HIPK2 targeting to the PML nuclear bodies and regulation of p53."
Exp. Cell Res. 317:1060-1070(2011) [PubMed] [Europe PMC] [Abstract]

"How cells switch HIPK2 on and off."
Cell Death Differ. 16:187-194(2009) [PubMed] [Europe PMC] [Abstract]

"Apoptosis and autophagy: Regulation of apoptosis by DNA damage signalling - roles of p53, p73 and HIPK2."
FEBS J. 276:6074-6083(2009) [PubMed] [Europe PMC] [Abstract]

"HIPK2-a therapeutical target to be (re)activated for tumor suppression: role in p53 activation and HIF-1? inhibition."
Cell Cycle 9:1270-1275(2010) [PubMed] [Europe PMC] [Abstract]

"Regulation of p53 activity by HIPK2: molecular mechanisms and therapeutical implications in human cancer cells."
Oncogene 29:4378-4387(2010) [PubMed] [Europe PMC] [Abstract]

"DNA damage-induced heterogeneous nuclear ribonucleoprotein K SUMOylation regulates p53 transcriptional activation."
J. Biol. Chem. 287:30789-30799(2012) [PubMed] [Europe PMC] [Abstract]

"An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]

"Patterns of somatic mutation in human cancer genomes."
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]