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Katsumi Kito

Publications and source records attributed to Katsumi Kito.

12 recordsLinked to original sources
PubMed2006

A Small Ras-like protein Ray/Rab1c modulates the p53-regulating activity of PRPK.

PRPK phosphorylates serine-15 residue of p53 and enhances transcriptional activity. PRPK possesses a bipartite nuclear localization signal and localizes in nucleus when over-expressed in cells. However, intrinsic PRPK localizes mainly in the cytosol in situ. While studying the mechanisms in the distribution of intrinsic PRPK, we identified a PRPK binding protein, an ubiquitously expressed Small Ras-like GTPase, Rab1c, also named Ray or Rab35. The over-expressed Ray was distributed in the nucleus, cytosol, and cell membrane. Both Ray wild type and GTP-restrictively binding mutant Ray-Q67L, but not guanine nucleotide unstable binding mutant Ray-N120I, partially distributed the over-expressed PRPK to the cytosol and also suppressed the PRPK-induced p53-transcriptional activity profoundly. A Small Ras-like GTPase protein Ray was thus indicated to modulate p53 transcriptional activity of PRPK.

Amino Acid Sequence↗
PubMed2006

Novel orthotopic implantation model of human malignant pleural mesothelioma (EHMES-10 cells) highly expressing vascular endothelial growth factor and its receptor.

Malignant pleural mesothelioma (MPM) is closely related to exposure to asbestos, and a rapid increase in the number of MPM patients in Japan is estimated in the years 2010-2050. The purpose of the present study was to establish a clinically relevant animal model that shows human patient-like progression of MPM. Here, we demonstrate that a human MPM cell line (EHMES-10) inoculated orthotopically (thoracic cavity) into severe combined immunodeficiency (SCID) mice produces highly vascularized thoracic tumors with pleural dissemination and bloody pleural effusions by 5 weeks, suggesting a patient-like progression of this cell line after orthotopic inoculation. EHMES-10 cells overexpressed vascular endothelial growth factor (VEGF), a molecule responsible for malignant effusions, and its receptor. Treatment with cisplatin, but not gemcitabine, significantly inhibited the production of pleural effusions, but it was not effective for thoracic tumors, consistent with chemotherapy refractory characteristics of MPM in patients. Our patient-like orthotopic model using EHMES-10 cells overexpressing VEGF and its receptor may be useful for examining the molecular pathogenesis of MPM and may contribute to the development of novel treatment strategies for MPM.

Animals↗
PubMed2006

NUB1 suppresses the formation of Lewy body-like inclusions by proteasomal degradation of synphilin-1.

NUB1 is a potent down-regulator of the ubiquitin-like protein NEDD8, because it targets NEDD8 to the proteasome for proteolytic degradation. From results in this study, we found that NUB1 physically interacts with synphilin-1 through its NEDD8-binding site, implying that NUB1 also targets synphilin-1 to the proteasome for degradation. Synphilin-1 is a major component of inclusion bodies found in the brains of patients with neurodegenerative alpha-synucleinopathies, including Parkinson's disease. In this study, we immunostained sections of brains from patients with Parkinson's disease and other alpha-synucleinopathies and demonstrated that NUB1, as well as synphilin-1, accumulates in the inclusion bodies. To define the role of NUB1 in the formation of these inclusion bodies, we performed a co-transfection assay using cultured HEK293 cells. This assay showed that NUB1 suppresses the formation of synphilin-1-positive inclusions. Further, biochemical assays revealed that NUB1 overexpression leads to the proteasomal degradation of synphilin-1. These results and our previous observations suggest that NUB1 indeed targets synphilin-1 to the proteasome for its efficient degradation, which, because of the resultant reduction in synphilin-1, suppresses the formation of synphilin-1-positive inclusions.

Adaptor Proteins, Signal Transducing↗
PubMed2005

AIP1/WDR1 supports mitotic cell rounding.

The actin cytoskeleton plays a fundamental role in configuring cell shapes and movements. Actin interacting protein 1 (AIP1)/tryptophan-aspartate-repeat protein 1 (WDR1) induces actin severing and disassembly cooperating with ADF/cofilin. We found that mitotic cell flattening but not rounding was manifested by suppression of AIP1/WDR1 in cells. This mitotic cell flattening was not due to any changes in phosphorylation and distribution of cofilin in cells. We carried out a direct observation of actin filament severing/disassembly assay and found that phosphorylated cofilin still somewhat severs/disassembles actin filaments and that AIP1/WDR1 effaces this in vitro. We suggest that the phosphorylation of ADF/cofilin will be insufficient to completely inhibit actin turnover during mitosis, and that AIP1/WDR1 could abort the severing/disassembly activity somewhat still carried out due to phosphorylated ADF/cofilin. This mechanism could be required to induce cell morphologic changes, especially mitotic cell rounding.

Actin Depolymerizing Factors↗
PubMed2005

Expression and phosphorylation of TOPK during spermatogenesis.

Among normal organs and tissues, the MAPKK-like mitotic protein kinase TOPK is expressed exclusively in the testis. We analyzed the expression and phosphorylation of TOPK to address the functional role of this kinase during spermatogenesis. TOPK protein is expressed mainly in the cytosol of spermatocytes and spermatids, but not in spermatids and spermatogonia in situ. TOPK-Thr-9, a cdk1/cyclin B target residue, was specifically phosphorylated during mitotic and meiotic phases, while TOPK-Thr-198, a key amino acid for the ATP pocket, was constantly phosphorylated irrespective of the cell cycle. These data indicate that spermatogenic germ cells with vital proliferation activity express TOPK. As TOPK-Thr-9 was phosphorylated during both mitosis and meiosis, TOPK was indicted to play a role in cytokinesis and/or chromosomal segregation but not in DNA replication.

Animals↗
PubMed2005

Hemoperitoneum secondary to spontaneous rupture of hepatic metastasis from lung cancer.

We describe a rare case of hemoperitoneum secondary to spontaneous rupture of hepatic metastasis from lung cancer. A 72-year-old man with non-small cell lung cancer was admitted to our hospital with sudden onset of right upper abdominal pain and hypovolemic shock. Laboratory tests showed severe anemia. Abdominal contrast-enhanced computed tomography revealed massive ascites and multiple liver metastases. Rupture of a metastatic liver tumor was suspected. Only palliative therapy was performed. The patient's general condition gradually worsened, and he died 2 months after admission. Autopsy examination revealed hemoperitoneum due to a ruptured metastatic liver tumor originating from pulmonary squamous cell carcinoma.

Aged↗
PubMed2005

Two cases of primary pulmonary osteosarcoma.

Two cases of primary pulmonary osteosarcoma are presented. In both cases, chest computed tomography revealed a calcified pulmonary mass and technetium-99m methylene diphosphonate bone scintigraphy showed intense uptake in the pulmonary mass. Primary pulmonary osteosarcoma was suspected on the basis of these radiographic findings. Microscopic examination of tumor specimens obtained by needle biopsy revealed histologic features of osteosarcoma, and this diagnosis was confirmed by postmortem examination of a second specimen in each case. Radiographic and histopathological findings enabled us to diagnose primary pulmonary osteosarcoma, which is one of the rarest types of cancer.

Aged↗
PubMed2004

Characterization of a MAPKK-like protein kinase TOPK.

A MAPKK-like protein kinase TOPK expresses in a wide range of proliferating cells and tissues such as cancer cells and testis. However, details of this kinase are still uncovered. We investigated the intracellular distribution of TOPK and its association with cdk1/cyclin B and microtubules. In interphase cells, TOPK expresses in cytosol and nucleus without any significant association with microtubule networks. During mitosis, TOPK-Thr-9 was phosphorylated by cdk1/cyclin B and TOPK significantly associates with mitotic spindles. When TOPK expression was suppressed, formation of spindle midzone was thinned and dimmed and cytokinesis was disturbed. We propose that TOPK plays a role in the formation of spindle midzone and in cytokinesis.

Animals↗
PubMed2003

Identification of CGI-121, a novel PRPK (p53-related protein kinase)-binding protein.

PRPK (p53-related protein kinase) has been reported as a novel protein kinase which binds to the tumor suppressor protein p53 and induces phosphorylation of p53 at Ser 15. To identify novel binding partners of PRPK, we performed a yeast two-hybrid screening and isolated an expressed sequence tag CGI-121 by which a 20-kDa protein was encoded. We demonstrated the protein-protein interaction of CGI-121 with PRPK in vivo and in vitro. The protein expression of CGI-121 was observed in many cell lines and was immunocytochemically identified in both the nucleus and cytosol. Although PRPK interacted with both CGI-121 and p53, several attempts to demonstrate an association between CGI-121 and p53 were unsuccessful. In addition, coprecipitation of p53 using recombinant PRPK was inhibited by adding recombinant CGI-121 in vitro, suggesting that CGI-121 could act as a potent inhibitor of the binding of PRPK to p53.

Amino Acid Sequence↗
PubMed2003

NEDD8 protein is involved in ubiquitinated inclusion bodies.

Proteolysis by the ubiquitin-proteasome system is considered to play a pathological role in several degenerative diseases that involve ubiquitinated inclusion bodies. In recent years, several ubiquitin-like proteins have been isolated, but it is uncertain whether their roles are associated with protein degradation through the ubiquitin-proteasome system. NEDD8 (neural precursor cell-expressed and developmentally down-regulated gene), which consists of 81 amino acid residues, possesses the highest sequence similarity to ubiquitin. Recent studies have indicated that NEDD8 is covalently ligated to cullin family proteins, which are components of certain ubiquitin E3 ligases, by a pathway analogous to that of ubiquitin. Thus, by focusing on the structural and functional association between NEDD8 and ubiquitin, it would be of interest to know whether the NEDD8 system is involved in pathological disorders of the ubiquitin-proteasome system. This study has examined the immunohistochemical distribution of NEDD8 protein by using a highly purified antibody in normal tissues and in tissues known to contain ubiquitinated inclusions. NEDD8 protein expression was widely observed in most types of tissues. Furthermore, accumulation of the NEDD8 protein was commonly observed in ubiquitinated inclusion bodies, including Lewy bodies in Parkinson's disease, Mallory bodies in alcoholic liver disease, and Rosenthal fibres in astrocytoma. Two of ten cases of neurofibrillary tangles and senile plaques from patients with Alzheimer's disease showed intense staining for NEDD8 as well as for ubiquitin. These findings suggest the possibility that the NEDD8 system is involved in the metabolism of these inclusion bodies via the ubiquitin-proteasome system.

Alzheimer Disease↗
PubMed2003

Rapid progression of primary cardiac leiomyosarcoma with obstruction of the left ventricular outflow tract and mitral stenosis.

We report a 73-year-old woman with primary cardiac leiomyosarcoma in the left atrium and ventricle. The tumor progressed very rapidly for 2 months after initial clinical evaluation. Obstruction of the left ventricular outflow tract and mitral stenosis were induced by the tumor. Urgent surgical resection was performed because she had cardiogenic shock due to paroxysmal atrial fibrillation. We could not resect the tumor completely because of severe invasion. She refused postoperative chemotherapy and radiotherapy, and died suddenly at home 89 days after surgery. To our knowledge, this is the first observation of mitral stenosis concomitant with obstruction of the left ventricular outflow tract in a patient with primary cardiac leiomyosarcoma.

Aged↗