A5058926295- DNA Repair Mechanisms
- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- Genomics and Chromatin Dynamics
- Cell death mechanisms and regulation
- Ubiquitin and proteasome pathways
- Cancer Research and Treatments
- Muscle Physiology and Disorders
- RNA Research and Splicing
- Genetics, Aging, and Longevity in Model Organisms
- RNA modifications and cancer
- Genetic Neurodegenerative Diseases
- Endoplasmic Reticulum Stress and Disease
- Protein Kinase Regulation and GTPase Signaling
- Epigenetics and DNA Methylation
- Mitochondrial Function and Pathology
- DNA and Nucleic Acid Chemistry
- Adipose Tissue and Metabolism
- Virus-based gene therapy research
- Monoclonal and Polyclonal Antibodies Research
- Signaling Pathways in Disease
- Reproductive Biology and Fertility
- Bacterial Genetics and Biotechnology
- Cancer-related gene regulation
- Neurogenetic and Muscular Disorders Research
Sapporo Medical University
2021-2023
Medical & Biological Laboratories (Japan)
1998-2020
Case Western Reserve University
2018
RIKEN Center for Computational Science
2008
Hokkaido University
2005-2006
Osaka City University
1999-2002
Japan Science and Technology Agency
2000-2001
Cycle (Germany)
2000
Howard Hughes Medical Institute
2000
Baylor College of Medicine
2000
The p53 tumor suppressor protein is activated and phosphorylated on serine-15 in response to various DNA damaging agents. gene product mutated ataxia telangiectasia, ATM, acts upstream of a signal transduction pathway initiated by ionizing radiation. Immunoprecipitated ATM had intrinsic kinase activity manganese-dependent manner. Ionizing radiation, but not ultraviolet rapidly enhanced this p53-directed endogenous ATM. These observations, along with the fact that phosphorylation radiation...
Chk1, an evolutionarily conserved protein kinase, has been implicated in cell cycle checkpoint control lower eukaryotes. By gene disruption, we show that CHK1 deficiency results a severe proliferation defect and death embryonic stem (ES) cells, peri-implantation lethality mice. Through analysis of conditional -deficient line, demonstrate ES cells lacking Chk1 have defective G 2 /M DNA damage response to γ-irradiation (IR). heterozygosity modestly enhances the tumorigenesis phenotype WNT-1...
Our recent work has shown that activation of the Ras/Raf/ERK pathway extends half-life Myc protein and thus enhances accumulation activity. We have extended these observations by investigating two N-terminal phosphorylation sites in Myc, Thr 58 Ser 62, which are known to be regulated mitogen stimulation. now show residues is critical for determining stability Myc. Phosphorylation 62 required Ras-induced stabilization likely mediated through action ERK. Conversely, 58, GSK-3 but dependent on...
The spinal muscular atrophies (SMAs), characterized by cord motor neuron depletion, are among the most common autosomal recessive disorders. One model of SMA pathogenesis invokes an inappropriate persistence normally occurring apoptosis. Consistent with this hypothesis, novel gene for neuronal apoptosis inhibitory protein (NAIP) has been mapped to region chromosome 5q13.1 and is homologous baculoviral inhibitor proteins. two first coding exons deleted in approximately 67% type I chromosomes...
Upon DNA damage, the amino terminus of p53 is phosphorylated at a number serine residues including S20, site that particularly important in regulating stability and function protein. Because no known kinase has been identified can modify this site, HeLa nuclear extracts were fractionated S20 phosphorylation was followed. We discovered activity copurifies with human homolog Schizosaccharomyces pombe checkpoint kinase, Chk1 (hCHK1). confirmed recombinant hCHK1, but not kinase-defective version...
The protein kinase Chk2, the mammalian homolog of budding yeast Rad53 and fission Cds1 checkpoint kinases, is phosphorylated activated in response to DNA damage by ionizing radiation (IR), UV irradiation, replication blocks hydroxyurea (HU). Phosphorylation activation Chk2 are ataxia telangiectasia-mutated (ATM) dependent IR, whereas phosphorylation ATM-independent when cells exposed or HU. Here we show that vitro , ATM phosphorylates Ser-Gln/Thr-Gln (SQ/TQ) cluster domain (SCD) on which...
Cdc7 kinase, conserved from yeasts to human, plays important roles in DNA replication. However, the mechanisms by which it stimulates initiation of replication remain largely unclear. We have analyzed phosphorylation MCM subunits during cell cycle examining mobility shift on SDS-PAGE. MCM4 chromatin undergoes specific S phase. phosphorylates complexes as well N-terminal polypeptide. Experiments with phospho-amino acid-specific antibodies indicate that phase-specific is due at (S/T)(S/T)P...
In the course of gene array studies aimed at identifying IFN-stimulated genes associated with interferon β (IFN-β)-induced apoptosis, we identified X-linked inhibitor apoptosis-associated factor-1 (<i>XAF1</i>) as a novel gene. XAF1 mRNA was up-regulated by IFN-α and IFN-β in all cells examined. However, IFNs induced high levels protein predominantly cell lines sensitive to proapoptotic effects IFN-β. apoptosis-resistant including WM164 melanoma, WM35 U937 pro-monocytic leukemia, HT1080...
The tumor suppressor protein p53 acts as a transcriptional activator that can mediate cellular responses to DNA damage by inducing apoptosis and cell cycle arrest. is nuclear phosphoprotein, phosphorylation has been proposed be means which the activity of regulated. cyclin-dependent kinase (CDK)-activating (CAK) was originally identified required for activation CDK-cyclin complex, CAK comprised three subunits: CDK7, cyclin H, p36MAT1. part transcription factor IIH multiprotein RNA polymerase...
huCdc7 encodes a catalytic subunit for<i>Saccharomyces cerevisae</i> Cdc7-related kinase complex of human. ASK, whose expression is cell cycle-regulated, binds and activates in cycle-dependent manner (Kumagai, H., Sato, N., Yamada, M., Mahony, D., Seghezzi, W., Lees, E., Arai, K., Masai, H. (1999) <i>Mol. Cell. Biol.</i> 19, 5083–5095). We have expressed complexed with ASK regulatory using the insect system. To facilitate purification complex, glutathione<i>S</i>-transferase (GST) was fused...
Human Lats2, a novel serine/threonine kinase, is member of the Lats kinase family that includes Drosophila tumour suppressor lats/warts . Lats1, counterpart phosphorylated in mitosis and localized to mitotic apparatus. However, regulation, function intracellular distribution Lats2 remain unclear. Here, we show phosphorylation target Aurora‐A kinase. We first showed residue S83 vitro Antibody recognizes this indicated also occurs vivo found transiently interacts with Aurora‐A, co‐localize at...
Microinjection of the restriction endonuclease HaeIII, which causes DNA double-strand breaks with blunt ends, induces nuclear accumulation p53 protein in normal and xeroderma pigmentosum (XP) primary fibroblasts. In contrast, this induction is not observed ataxia telangiectasia (AT) HaeIII-induced fibroblasts phosphorylated at serine 15, as determined by immunostaining an antibody specific for 15 p53. This phosphorylation correlates well accumulation. Treatment lactacystin (an inhibitor...
DNA polymerase lambda (Pol lambda) was recently identified as a new member of the family X polymerases in eukaryotic cells. Pol contains nuclear localization signal (NLS), BRCA1-C terminal (BRCT) domain, proline-rich region, helix-hairpin-helix (HhH) and pol motifs. Since amino acid sequence for shares high degree homology to beta, is considered have similar enzymatic nature beta.Recombinant human shown possess template-directed activity its monomeric form. required either Mn2+ or Mg2+ metal...
Background The c‐ myc proto‐oncogene has been suggested to play key roles in cell proliferation, differentiation, transformation and apoptosis. A variety of functions C‐MYC, the product , are attributed protein–protein interactions with various cellular factors including Max, YY1, p107, Bin1 TBP. Max YY1 bind C‐terminal region while TBP N‐terminal covering boxes. is involved all biological different proteins therefore thought interact C‐MYC display functions. Results We cloned two cDNAs...
The gonad arms of C. elegans hermaphrodites acquire invariant shapes by guided migrations distal tip cells (DTCs), which occur in three phases that differ the direction and basement membrane substrata used for movement. We found mig-6 encodes long (MIG-6L) short (MIG-6S) isoforms extracellular matrix protein papilin, each required distinct aspects DTC migration. Both MIG-6 have a predicted N-terminal papilin cassette, lagrin repeats C-terminal Kunitz-type serine proteinase inhibitory...