Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A novel family of cofactors that differentially interact with homeoproteins have been identified via a yeast two-hybrid screen. The proteins contain a conserved protein kinase domain that is separated from a domain that interacts with homeoproteins and hence are termed homeodomain-interacting protein kinases (HIPKs): HIPK1, HIPK2, and HIPK3. We show that HIPKs are nuclear kinases using GFP-HIPK fusion constructs. The DNA binding activity of the NK-3 homeoprotein is greatly enhanced by HIPK2, but this effect is independent of its phosphorylation by HIPK2. In cultured cells, HIPKs localize to nuclear speckles and potentiate the repressor activities of NK homeoproteins. The co-repressor activity of HIPKs depends on both its homeodomain interaction domain and a co-repressor domain that maps to the N terminus. Thus, HIPKs represent a heretofore undescribed family of co-repressors for homeodomain transcription factors.
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PMID:Homeodomain-interacting protein kinases, a novel family of co-repressors for homeodomain transcription factors. 974 62

HIPK2 has been described as a homoedomain-interacting protein kinase with a nuclear localization. Here we describe that HIPK2 can also associate with TRADD, a protein that interacts with tumor necrosis factor receptor type 1 (TNF-R1). Under the conditions where HIPK2/TRADD association was found, no direct interaction of HIPK2 with CD95, TNF-R1, FADD or caspase-8 could be detected. Therefore, HIPK2 may play a role in TNF-R1 mediated signaling.
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PMID:The serine/threonine kinase HIPK2 interacts with TRADD, but not with CD95 or TNF-R1 in 293T cells. 1103 52

Here we identified the human serine/threonine kinase HIPK2 as a novel member of the DYRK kinase subfamily. Alignment of several DYRK family proteins including the kinases minibrain, MJAK, PKY, the Dictyostelium kinase YakA and Saccharomyces YAK1 allowed the identification of several evolutionary conserved DYRK consensus motifs within the kinase domain. A lysine residue conserved between all DYRK kinase family members was found to be essential for the kinase function of HIPK2. Human HIPK2 was mapped to chromosome 7q32-q34 and murine HIPK2 to chromosome 6B, the homologue to human chromosome 7.
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PMID:Human homeodomain-interacting protein kinase-2 (HIPK2) is a member of the DYRK family of protein kinases and maps to chromosome 7q32-q34. 1112 Mar 54

HIPK2 (homeodomain-interacting protein kinase 2) is a CD95 binding partner in yeast. Its primary amino acid sequence is highly conserved between human and mouse. The highest HIPK2 mRNA expression is found in neuronal tissue. The HIPK2 gene is located on human chromosome 7q33-35 and the protein is mainly localized in the nucleus. HIPK2 has been described to play a role as a co-repressor for homeodomain transcription factors.
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PMID:Isolation and characterization of cDNAs for the protein kinase HIPK2. 1126 74

The HIPK2 protein is a member of a recently identified family of nuclear protein kinases that interact with homeodomain transcription factors and that are well conserved in various organisms. HIPK2 acts as a transcriptional co-repressor of homeoproteins and it is a component of a co-repressor complex containing Groucho and a histone deacetylase. We have recently demonstrated that the HIPK2 protein interacts with HMGA1 proteins in vitro and in vivo and that HIPK2 exerts a potent inhibitory effect on the cell growth of different normal cell lines. Here we demonstrate that the HIPK2 gene is expressed during the latest phases of embryogenesis, and preferentially in retina, in muscle and in neural tissues. Conversely, HIPK2 is ubiquitously expressed in murine and human adult tissues. We have also found that HIPK2 expression is reduced in breast and thyroid carcinomas, suggesting a role of this gene in the process of carcinogenesis.
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PMID:The homeodomain-interacting protein kinase 2 gene is expressed late in embryogenesis and preferentially in retina, muscle, and neural tissues. 1179 64

Here we demonstrate that endogenous human homeodomain-interacting protein kinase (HIPK) 2 and the highly homologous kinase HIPK3 are found in a novel subnuclear domain, the HIPK domains. These are distinct from other subnuclear structures such as Cajal bodies and nucleoli and show only a partial colocalization with promyelocytic leukemia (PML) nuclear bodies (PML-NBs). A kinase inactive HIPK2 point mutant is localized in the nucleoplasm. The occurrence of HIPK domains in PML-/- fibroblasts reveals their independence from the PML protein. HIPK2 can be almost completely recruited to PML-NBs by the PML isoform PML IV, but not by PML-III. PML IV-mediated recruitment of HIPK2 does not rely on its kinase function and also occurs in PML-/- fibroblasts, showing that this PML isoform is sufficient for recruitment of HIPK2. Whereas the architecture of HIPK domains is PML independent, HIPK2-mediated enhancement of p53-dependent transcription, p53 serine 46 phosphorylation and the antiproliferative function of HIPK2 strictly rely on the presence of PML.
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PMID: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. 1290 96

Ser-46 of p53 is phosphorylated in response to DNA-damage in vivo, and it plays a pivotal role for apoptotic signaling by p53 through regulating the transcriptional activation of genes involved in apoptosis. We found that the presence of the nitric oxide (NO) donor S-nitroso-N-acetyl-D,L-penicillamine (200-800 microM) during UV-irradiation of MCF-7 cells resulted in a significant reduction in the Ser-46 phosphorylation, compared to the UV-irradiated cells without NO. This reduction occurred independently of cyclic GMP generation and without affecting activities of p53 kinases such as the PI3K family, p38 MAPK, and HIPK2. The presence of NO was found to protect HCT116 human colon tumor cells containing wild-type p53 from UV-induced apoptosis, whereas no apparent inhibitory effect of NO on UV-induced apoptosis was observed in those deficient in p53. Our results suggest that NO-mediated protection of apoptosis is p53-dependent, occurring at least partly through NO-inhibition of phosphorylation of p53 on Ser-46.
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PMID:Nitric oxide prevents UV-induced phosphorylation of the p53 tumor-suppressor protein at serine 46: a possible role in inhibition of apoptosis. 1292 14

We performed yeast two-hybrid screening of a human kidney cell cDNA library to study the biological role of the hantavirus nucleocapsid protein (NP). We found that Seoul virus (SEOV) and Hantaan virus (HTNV) NPs were associated with small ubiquitin-like modifier (SUMO)-1-interacting proteins PIAS1, PIASxbeta, HIPK2, CHD3, and TTRAP, which interacted with the SUMO-1 conjugating enzyme (Ubc-9) and SUMO-1 in the yeast two-hybrid assay. Interactions between the HIPK2, CHD3, and TTRAP proteins and SEOV NP were also shown in a mammalian two-hybrid assay. However, there was no interaction between PIAS proteins and NP, which was probably due to the inhibitory effect of PIAS on transcription in the mammalian two-hybrid assay. Nevertheless, a co-expression experiment suggested the existence of a PIAS-NP interaction in the cytoplasm. The region spanning amino acids 100-125 of SEOV NP, which represents a critical region for NP-NP polymerization, was found to be responsible for the interaction with SUMO-1-related molecules in both the yeast and mammalian two-hybrid assays. These results add to the information on interactions of hantavirus NP and host cellular proteins.
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PMID:Association of the nucleocapsid protein of the Seoul and Hantaan hantaviruses with small ubiquitin-like modifier-1-related molecules. 1460 33

Promyelocytic leukemia nuclear bodies (PML-NBs) are discrete interchromosomal macromolecular structures. The integrity of this dynamic nuclear subcompartment critically depends on the presence of the name-giving PML protein. Among the permanent or transient residents of PML-NBs are various regulatory proteins, including Sp100, CBP, pRb, HIPK2, RAD51 and p53. PML-NBs are frequently targeted by viral infections, as a number of different RNA and DNA viruses, including herpesviruses, adenoviruses, papovaviruses, papillomaviruses and arenaviruses, cause changes in PML-NBs. Viruses interfere with PML-NB in two ways: 1) some viral proteins can associate with PML-NB proteins and/or lead to the destruction and lysis of this subnuclear compartment, thus aiding viral gene expression and disabling the host's innate immunity; 2) the parental genomes of some nuclear-replicating DNA viruses associate preferentially with PML-NBs, which presumably serves to assist in viral gene expression or replication. Here we feature the different viral strategies leading to the hijacking of PML-NBs and discuss the consequences for the immune response.
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PMID:Viruses as hijackers of PML nuclear bodies. 1462 29

HIPK2 shows overlapping localization with p53 in promyelocytic leukemia (PML) nuclear bodies (PML-NBs) and functionally interacts with p53 to increase gene expression. Here we demonstrate that HIPK2 and the PML-NB resident protein Sp100 synergize for the activation of p53-dependent gene expression. Sp100 and HIPK2 interact and partially colocalize in PML-NBs. The cooperation of HIPK2 and Sp100 for the induction of p21(Waf1) is completely dependent on the presence of p53 and the kinase function of HIPK2. Downregulation of Sp100 levels by expression of siRNA does not interfere with p53-mediated transcription, but obviates the enhancing effect of HIPK2. In summary, these experiments reveal a novel function for Sp100 as a coactivator for HIPK2-mediated p53 activation.
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PMID:Sp100 is important for the stimulatory effect of homeodomain-interacting protein kinase-2 on p53-dependent gene expression. 1464 68


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