Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Ki-1 antibody not only detects a Hodgkin-associated membrane molecule of 120 kd (Ki-1/120 = CD30), but also reacts with an independently synthesized molecule of 57 kd (Ki-1/57) that only occurs intracellularly. Hodgkin's disease-derived cell lines L428 and L540 contain both Ki-1-reactive antigens, whereas others, e.g., U266/Bl myeloma cells, only express the intracellular Ki-1/57. The present immunoelectronmicroscopic analysis detected the Ki-1/57 antigen of U266/Bl cells not only in the cytoplasm, but also in association with the nuclear envelope, chromatin structures, and nucleoli. This Ki-1/57-specific type of labeling also was observed in L428 and L540 cells that, in contrast to U266/Bl cells, showed an additional staining of cell membranes and cytoplasmic vesicles. These results were confirmed by two independent methods: 1) cytocentrifuge preparations of isolated nuclei of L540 cells showed a spotted Ki-1-specific labeling, 2) immunoprecipitations demonstrated that the Ki-1/57, but not the Ki-1/120 antigen, was transferred into the nuclei of L540 and U266/Bl cells, whereas the Ki-1/120 antigen with its 90-kd precursor remained in the non-nuclei fraction of L540 cells.
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PMID:Cellular localizations and processing of the two molecular forms of the Hodgkin-associated Ki-1 (CD30) antigen. The protein kinase Ki-1/57 occurs in the nucleus. 131 Aug 32

The Hodgkin-associated Ki-1 antigen (CD30) consists of a 120-kDa membrane-associated glycosylated phosphoprotein (Ki-1/120) and a 57-kDa non-glycosylated phosphoprotein (Ki-1/57) which only occurs intracellularly. Both molecules are phosphorylated at serine residues. An analysis of the peptide fragments resulting from staphylococcal V8-protease digestion of the Ki-1/57 molecule revealed identical bands irrespective of the cell source. Only a few bands of the Ki-1/57 digests appeared among the peptide fragments of the Ki-1/120 membrane antigen. The protein kinase activity was tested for both forms of the Ki-1 antigen. The Ki-1/120, devoid of the Ki-1/57 molecule, was immunoprecipitated from cell lysates of Hodgkin-analogous cell lines L428 or L540, which had been loaded with the Ki-1 or the Ki-1-analogous antibodies Ber-H2, HSR-1, -2 and -3 (method 1). These other antibodies reacted with the Ki-1/120, but not with the Ki-1/57 antigen. The latter, devoid of the Ki-1/120, was isolated from L540 cells after removal of the membrane form by method 1 or from U266/Bl myeloma or Raji Burkitt lymphoma cells which only contain the smaller form. Effects of non-specific adsorption were eliminated by various control precipitates. The Ki-1/57 intracellular antigen showed autophosphorylation and could phosphorylate histones as well. In contrast, a protein kinase activity of the membrane-associated Ki-1/120 could not be demonstrated.
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PMID:Protein kinase activity of the intracellular but not of the membrane-associated form of the Ki-1 antigen (CD30). 216 Nov 15

A novel antigen was identified by the cross-reactivity of the anti-CD30 antibody Ki-1. This 57-kD intracellular Ki-1 antigen (Ki-1/57) is induced upon activation of leukocytes and is transported to the nuclear compartment. We describe the partial cloning and sequencing of the Ki-1/57 cDNA from a lambda gt 11-cDNA library derived from the Hodgkin-analogous cell line L540. New monoclonal antibodies were produced against the recombinant Ki-1/57 protein fragment which were used to confirm that the Ki-1/57 antigen is associated with kinase activity and is expressed in a variety of tumor cell lines and in activated but not resting leukocytes. The Ki-1/57 gene was mapped to the bands 9q22.3-31 of human chromosome 9. This is an area which appears to be associated with secondary chromosomal aberrations in acute myeloid leukemias.
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PMID:Characterization, mapping and partial cDNA sequence of the 57-kD intracellular Ki-1 antigen. 952 63

Ki-1/57, the 57-kDa human protein antigen recognized by the CD30 antibody Ki-1, is a cytoplasmic and nuclear protein that is phosphorylated on serine and threonine residues. When isolated from the Hodgkin's lymphoma analogous cell line L540 Ki-1/57 co-immunoprecipitated with a Thr/Ser protein kinase activity. It has been also found to interact with hyaluronic acid and has therefore been termed intracellular IHABP4 (hyaluronan-binding protein 4). Recent studies demonstrated, however, that Ki-1/57 engages in specific interaction with the chromo-helicase-DNA-binding domain protein 3, a nuclear protein involved in chromatin remodeling and transcription regulation. We used the yeast two-hybrid system to find proteins interacting with Ki-1/57 and identified the adaptor protein RACK1 (receptor of activated kinase 1). Next, we confirmed this interaction in vitro and in vivo, performed detailed mapping studies of the interaction sites of Ki-1/57 and RACK-1, and demonstrated that Ki-1/57 also co-precipitates with protein kinase C (PKC) when isolated from phorbol 12-myristate 13-acetate (PMA)-activated L540 tumor cells and is a substrate for PKC phosphorylation in vitro and in vivo. Interestingly, the interaction of Ki-1/57 with RACK1 is abolished upon activation of L540 cells with PMA, which results in the phosphorylation of Ki-1/57 and its exit from the nucleus. Taken together, our data suggest that Ki-1/57 forms a stable complex with RACK-1 in unstimulated cells and upon PMA stimulation gets phosphorylated on threonine residues located at its extreme C terminus. These events associate Ki-1/57 with the RACK1/PKC pathway and may be important for the regulation of its cellular functions.
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PMID:Ki-1/57 interacts with RACK1 and is a substrate for the phosphorylation by phorbol 12-myristate 13-acetate-activated protein kinase C. 1469 38

Ki-1/57 is a cytoplasmic and nuclear phospho-protein of 57 kDa and interacts with the adaptor protein RACK1, the transcription factor MEF2C, and the chromatin remodeling factor CHD3, suggesting that it might be involved in the regulation of transcription. Here, we describe yeast two-hybrid studies that identified a total of 11 proteins interacting with Ki-1/57, all of which interact or are functionally associated with p53 or other members of the p53 family of proteins. We further found that Ki-1/57 is able to interact with p53 itself in the yeast two-hybrid system when the interaction was tested directly. This interaction could be confirmed by pull down assays with purified proteins in vitro and by reciprocal co-immunoprecipitation assays from the human Hodgkin analogous lymphoma cell line L540. Furthermore, we found that the phosphorylation of p53 by PKC abolishes its interaction with Ki-1/57 in vitro.
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PMID:Evidence for the interaction of the regulatory protein Ki-1/57 with p53 and its interacting proteins. 1645 55

The human protein Ki-1/57 was first identified through the cross reactivity of the anti-CD30 monoclonal antibody Ki-1, in Hodgkin lymphoma cells. The expression of Ki-1/57 in diverse cancer cells and its phosphorylation in peripheral blood leukocytes after mitogenic activation suggested its possible role in cell signaling. Ki-1/57 interacts with several other regulatory proteins involved in cellular signaling, transcriptional regulation and RNA metabolism, suggesting it may have pleiotropic functions. In a previous spectroscopic analysis, we observed a low content of secondary structure for Ki-1/57 constructs. Here, Circular dichroism experiments, in vitro RNA binding analysis, and limited proteolysis assays of recombinant Ki-1/57(122-413) and proteolysis assays of endogenous full length protein from human HEK293 cells suggested that Ki-1/57 has characteristics of an intrinsically unstructured protein. Small-angle X-ray scattering (SAXS) experiments were performed with the C-terminal fragment Ki-1/57(122-413). These results indicated an elongated shape and a partially unstructured conformation of the molecule in solution, confirming the characteristics of an intrinsically unstructured protein. Experimental curves together with ab initio modeling approaches revealed an extended and flexible molecule in solution. An elongated shape was also observed by analytical gel filtration. Furthermore, sedimentation velocity analysis suggested that Ki-1/57 is a highly asymmetric protein. These findings may explain the functional plasticity of Ki-1/57, as suggested by the wide array of proteins with which it is capable of interacting in yeast two-hybrid interaction assays.
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PMID:Human regulatory protein Ki-1/57 has characteristics of an intrinsically unstructured protein. 1878 74

The cytoplasmic and nuclear protein Ki-1/57 was first identified in malignant cells from Hodgkin's lymphoma. Despite studies showing its phosphorylation, arginine methylation, and interaction with several regulatory proteins, the functional role of Ki-1/57 in human cells remains to be determined. Here, we investigated the relationship of Ki-1/57 with RNA functions. Through immunoprecipitation assays, we verified the association of Ki-1/57 with the endogenous splicing proteins hnRNPQ and SFRS9 in HeLa cell extracts. We also found that recombinant Ki-1/57 was able to bind to a poly-U RNA probe in electrophoretic mobility shift assays. In a classic splicing test, we showed that Ki-1/57 can modify the splicing site selection of the adenoviral E1A minigene in a dose-dependent manner. Further confocal and fluorescence microscopy analysis revealed the localization of enhanced green fluorescent proteinKi-1/57 to nuclear bodies involved in RNA processing and or small nuclear ribonucleoprotein assembly, depending on the cellular methylation status and its N-terminal region. In summary, our findings suggest that Ki-1/57 is probably involved in cellular events related to RNA functions, such as pre-mRNA splicing.
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PMID:Functional association of human Ki-1/57 with pre-mRNA splicing events. 1952 14

Ki-1/57 is a cytoplasmic and nuclear protein of 57 kDa first identified in malignant cells from Hodgkin's lymphoma. Based on yeast-two hybrid protein interaction we found out that Ki-1/57 interacts with adaptor protein RACK1 (receptor of activated kinase 1), CIRP (cold-inducible RNA-binding protein), RPL38 (ribosomal protein L38) and FXR1 (fragile X mental retardation-related protein 1). Since these proteins are involved in the regulation of translation we suspected that Ki-1/57 may have a role in it. We show by immunoprecipitation the association of Ki-1/57 with FMRP. Confocal microscopy revealed that Ki-1/57 colocalizes with FMRP/FXR1/2 to stress granules. Furthermore Ki-1/57 cosediments with free ribosomal particles and enhances translation, when tethered to a reporter mRNA, suggesting that Ki-1/57 may be involved in translational regulation.
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PMID:Evidence for the association of the human regulatory protein Ki-1/57 with the translational machinery. 2177 94

Ki-1/57 is a nuclear and cytoplasmic regulatory protein first identified in malignant cells from Hodgkin's lymphoma. It is involved in gene expression regulation on both transcriptional and mRNA metabolism levels. Ki-1/57 belongs to the family of intrinsically unstructured proteins and undergoes phosphorylation by PKC and methylation by PRMT1. Previous characterization of its protein interaction profile by yeast two-hybrid screening showed that Ki-1/57 interacts with proteins of the SUMOylation machinery, the SUMO E2 conjugating enzyme UBC9 and the SUMO E3 ligase PIAS3, which suggested that Ki-1/57 could be involved with this process. Here we identified seven potential SUMO target sites (lysine residues) on Ki-1/57 sequence and observed that Ki-1/57 is modified by SUMO proteins in vitro and in vivo. We showed that SUMOylation of Ki-1/57 occurred on lysines 213, 276, and 336. In transfected cells expressing FLAG-Ki-1/57 wild-type, its paralog FLAG-CGI-55 wild-type, or their non-SUMOylated triple mutants, the number of PML-nuclear bodies (PML-NBs) is reduced compared with the control cells not expressing the constructs. More interestingly, after treating cells with arsenic trioxide (As2O3), the number of PML-NBs is no longer reduced when the non-SUMOylated triple mutant Ki-1/57 is expressed, suggesting that the SUMOylation of Ki-1/57 has a role in the control of As2O3-induced PML-NB formation. A proteome-wide analysis of Ki-1/57 partners in the presence of either SUMO-1 or SUMO-2 suggests that the involvement of Ki-1/57 with the regulation of gene expression is independent of the presence of either SUMO-1 or SUMO-2; however, the presence of SUMO-1 strongly influences the interaction of Ki-1/57 with proteins associated with cellular metabolism, maintenance, and cell cycle.
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PMID:Human Regulatory Protein Ki-1/57 Is a Target of SUMOylation and Affects PML Nuclear Body Formation. 2869 42