Research Topics
Genomes and Genes
| Shigetsugu HatakeyamaSummaryAffiliation: Kyushu University Country: Japan Publications
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Detail Information
Publications
Degradation of p57Kip2 mediated by SCFSkp2-dependent ubiquitylationTakumi Kamura
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka, Fukuoka 812 8582, Japan
Proc Natl Acad Sci U S A 100:10231-6. 2003..These observations thus demonstrate that the SCFSkp2 complex plays an important role in cell-cycle progression by determining the abundance of p57Kip2 and that of the related CDK inhibitor p27Kip1...
U-box proteins as a new family of ubiquitin ligasesShigetsugu Hatakeyama
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka, Fukuoka 812 8582, Japan
Biochem Biophys Res Commun 302:635-45. 2003..We here review recent progress in the characterization of U-box proteins and of their role in the quality control system that underlies the cellular stress response to the intracellular accumulation of abnormal proteins...
Ubiquitylation as a quality control system for intracellular proteinsShigetsugu Hatakeyama
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka
J Biochem 134:1-8. 2003..This review addresses recent progress in characterization of the role of E3 enzymes, especially that of U-box proteins, in quality control of intracellular proteins...
Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7Masayoshi Yada
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Maidashi, Higashi ku, Fukuoka, Fukuoka, Japan
EMBO J 23:2116-25. 2004..Accumulation of c-Myc was also apparent in mouse Fbw7-/- embryonic stem cells. These observations suggest that two F-box proteins, Fbw7 and Skp2, differentially regulate c-Myc stability by targeting MB1 and MB2, respectively...
Functional regulation of FEZ1 by the U-box-type ubiquitin ligase E4B contributes to neuritogenesisFumihiko Okumura
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka 812 8582, Japan
J Biol Chem 279:53533-43. 2004..These findings indicate that E4B serves as a ubiquitin ligase for FEZ1 and thereby regulates its function but not its degradation...
Cytoplasmic ubiquitin ligase KPC regulates proteolysis of p27(Kip1) at G1 phaseTakumi Kamura
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka, Fukuoka 812 8582, Japan
Nat Cell Biol 6:1229-35. 2004..Depletion of KPC1 by RNA interference also inhibited p27(Kip1) degradation. KPC thus probably controls degradation of p27(Kip1) in G1 phase after export of the latter from the nucleus...
Interaction of U-box-type ubiquitin-protein ligases (E3s) with molecular chaperonesShigetsugu Hatakeyama
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka, Fukuoka 812 8582, Japan
Genes Cells 9:533-48. 2004..These observations suggest that the function of U box-type E3s is to mediate the degradation of unfolded or misfolded proteins in conjunction with molecular chaperones as receptors that recognize such abnormal proteins...
U-box protein carboxyl terminus of Hsc70-interacting protein (CHIP) mediates poly-ubiquitylation preferentially on four-repeat Tau and is involved in neurodegeneration of tauopathyShigetsugu Hatakeyama
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Fukuoka, Japan
J Neurochem 91:299-307. 2004..Thus, CHIP is a ubiquitin ligase for four-repeat tau and maintains neuronal survival by regulating the quality control of tau in neurons...
Noncovalent SUMO-1 binding activity of thymine DNA glycosylase (TDG) is required for its SUMO-1 modification and colocalization with the promyelocytic leukemia proteinHidehisa Takahashi
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka, Fukuoka 812 8582, Japan
J Biol Chem 280:5611-21. 2005..These results suggest that SUMO-1 functions to tether proteins to PML-containing nuclear bodies through post-translational modification and noncovalent protein-protein interaction...
Molecular clearance of ataxin-3 is regulated by a mammalian E4Masaki Matsumoto
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
EMBO J 23:659-69. 2004..These observations suggest that E4 is a rate-limiting factor in the degradation of pathological forms of ataxin-3, and that targeted expression of E4B is a potential gene therapy for SCA3...
Large-scale analysis of the human ubiquitin-related proteomeMasaki Matsumoto
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Fukuoka, Japan
Proteomics 5:4145-51. 2005..Our results demonstrate the potential of proteomics analysis of protein ubiquitylation to provide important insight into the regulation of protein stability and other ubiquitin-related cellular functions...
Mammalian E4 is required for cardiac development and maintenance of the nervous systemChie Kaneko-Oshikawa
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Higashi ku, Fukuoka, Japan
Mol Cell Biol 25:10953-64. 2005..UFD2a thus appears to be essential for the development of cardiac muscle, as well as for the protection of spinocerebellar neurons from degeneration induced by endoplasmic reticulum stress...
Large-scale proteomic analysis of tyrosine-phosphorylation induced by T-cell receptor or B-cell receptor activation reveals new signaling pathwaysMasaki Matsumoto
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Fukuoka, Japan
Proteomics 9:3549-63. 2009..Thus comparative and quantitative studies of tyrosine-phosphorylation have the potential to expand knowledge of signaling networks and to promote understanding of signal transduction at the system level...
Mouse Fbw7/Sel-10/Cdc4 is required for notch degradation during vascular developmentRyosuke Tsunematsu
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
J Biol Chem 279:9417-23. 2004..Expression of Notch1, -2, or -3 or of cyclin E was unaffected in Fbw7(-/-) embryos. Mammalian Fbw7 thus appears to play an indispensable role in negative regulation of the Notch4-Hey1 pathway and is required for vascular development...
Preferential interaction of TIP120A with Cul1 that is not modified by NEDD8 and not associated with Skp1Kiyotaka Oshikawa
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka, Japan
Biochem Biophys Res Commun 303:1209-16. 2003..These observations thus suggest that TIP120A may function as a negative regulator of the SCF complex by binding to nonneddylated Cul1 and thereby preventing assembly of this ubiquitin ligase...
Skp2-mediated degradation of p27 regulates progression into mitosisKeiko Nakayama
National Institute of Advanced Industrial Science and Technology AIST, Biological Information Research Center, Tokyo 135 0064, Japan
Dev Cell 6:661-72. 2004..These data suggest that p27 proteolysis is necessary for the activation of not only Cdk2 but also Cdc2, and that Skp2 contributes to regulation of G(2)-M progression by mediating the degradation of p27...
Impaired degradation of inhibitory subunit of NF-kappa B (I kappa B) and beta-catenin as a result of targeted disruption of the beta-TrCP1 geneKeiko Nakayama
Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka 812 8582, Japan
Proc Natl Acad Sci U S A 100:8752-7. 2003..In addition, they implicate beta-TrCP1 in the maintenance of ploidy during cell-cycle progression...
Characterization of the mouse gene for the U-box-type ubiquitin ligase UFD2aChie Kaneko
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka, Fukuoka, 812 8582, Japan
Biochem Biophys Res Commun 300:297-304. 2003..We also show that UFD2a interacts with VCP (a AAA-family ATPase) that is thought to mediate protein folding. These data implicate UFD2a in the degradation of neuronal proteins by the ubiquitin-proteasome pathway...
Formation of Mallory body-like inclusions and cell death induced by deregulated expression of keratin 18Ikuo Nakamichi
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812 8582, Japan
Mol Biol Cell 13:3441-51. 2002..Deregulated expression of K18, or an imbalance between K8 and K18, may thus be an important determinant of MB formation, which compromises the function of centrosomes and the microtubule network and leads to cell death...
Increased proliferation of B cells and auto-immunity in mice lacking protein kinase CdeltaAkimoto Miyamoto
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812 8582, Japan
Nature 416:865-9. 2002..These results suggest that PKC-delta has an indispensable function in negative regulation of B-cell proliferation, and is particularly important for the establishment of B-cell tolerance...
Degradation of Tob1 mediated by SCFSkp2-dependent ubiquitinationYoshihiro Hiramatsu
Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan
Cancer Res 66:8477-83. 2006..Moreover, cyclin D1 expression was suppressed in Skp2 knockdown HeLa cells. These data suggest that Tob1 is a novel target for degradation by the SCF-Skp2 ubiquitin ligase...
Ro52 functionally interacts with IgG1 and regulates its quality control via the ERAD systemMutsumi Takahata
Department of Biochemistry, Hokkaido University Graduate School of Medicine, N15 W7, Kita ku, Sapporo, Hokkaido 060 8638, Japan
Mol Immunol 45:2045-54. 2008..Taken together, our findings suggest that Ro52 plays a significant role in quality control of IgG1 through the ERAD system...
Identification of developmentally expressed proteins that functionally interact with Nedd4 ubiquitin ligaseRodolfo Murillas
Experimental Immunology Branch, NCI, National Institutes of Health, Bethesda, Maryland 20892 1360, USA
J Biol Chem 277:2897-907. 2002..However, this protein clearly associates with Nedd4 through its PY domains and can alter the location of Nedd4 in cells, suggesting a role other than as a ubiquitylation substrate...
Ubiquitylation and degradation of serum-inducible kinase by hVPS18, a RING-H2 type ubiquitin ligaseSatomi Yogosawa
Department of Neurochemistry, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187 8502, Japan
J Biol Chem 280:41619-27. 2005..Furthermore, the delayed entry into S phase is observed in HeLa cells overexpressing hVPS18. These results suggest that hVPS18 may play an important role in regulation of SNK activity through its ubiquitin ligase...
CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activityYuzuru Imai
Laboratory for Motor System Neurodegeneration, RIKEN Brain Science Institute, Saitama 351 0198, Japan
Mol Cell 10:55-67. 2002..Furthermore, CHIP enhanced the ability of Parkin to inhibit cell death induced by Pael-R. Taken together, these results indicate that CHIP is a mammalian E4-like molecule that positively regulates Parkin E3 activity...
[Neurodegenerative diseases regulated by ubiquitin-proteasome system]Shigetsugu Hatakeyama
Department of Molecular Biochemistry, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Japan
Seikagaku 77:389-99. 2005
CHIP promotes proteasomal degradation of familial ALS-linked mutant SOD1 by ubiquitinating Hsp/Hsc70Makoto Urushitani
Laboratory for Motor System Neurodegeneration, RIKEN Brain Science Institute, Wako, Saitama, Japan
J Neurochem 90:231-44. 2004..Taken together, we propose a novel pathway in which ubiquitinated Hsp/Hsc70 might deliver mutant SOD1 to, and facilitate its degradation, at the proteasome...
Subcellular expression of autoimmune regulator is organized in a spatiotemporal mannerHiroko Akiyoshi
Division of Molecular Immunology, Institute for Enzyme Research, University of Tokushima, Tokushima 770 8503, Japan
J Biol Chem 279:33984-91. 2004..These results suggest that the transcriptional regulating activities of AIRE within a cell are controlled and organized in a spatiotemporal manner...
Targeted destruction of c-Myc by an engineered ubiquitin ligase suppresses cell transformation and tumor formationShigetsugu Hatakeyama
Department of Molecular Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Japan
Cancer Res 65:7874-9. 2005..These findings indicate that the targeted destruction of c-Myc by an artificial E3 may represent an effective therapeutic strategy for certain human malignancies...
Tripartite motif protein 32 facilitates cell growth and migration via degradation of Abl-interactor 2Satoshi Kano
Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
Cancer Res 68:5572-80. 2008..These findings suggest that TRIM32 is a novel oncogene that promotes tumor growth, metastasis, and resistance to anticancer drugs...
TRIM68 regulates ligand-dependent transcription of androgen receptor in prostate cancer cellsNaoto Miyajima
Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Japan
Cancer Res 68:3486-94. 2008..These results indicate that TRIM68 functions as a cofactor for AR-mediated transcription and is likely to be a novel diagnostic tool and a potentially therapeutic target for prostate cancer...
Ubiquitylation of epsilon-COP by PIRH2 and regulation of the secretion of PSASatoru Maruyama
Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
Mol Cell Biochem 307:73-82. 2008..Our results indicate that PIRH2 functions as a regulator for COP I complex...
Involvement of Rabring7 in EGF receptor degradation as an E3 ligaseAyuko Sakane
Department of Biochemistry, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770 8503, Japan
Biochem Biophys Res Commun 357:1058-64. 2007..These results suggest that Rabring7 is involved in the endocytic trafficking of EGFR through its E3 ligase activity...
[Neurodegenerative diseases regulated by ubiquitin-proteasome system]Shigetsugu Hatakeyama
Department of Molecular Biochemistry, Hokkaido University Graduate School of Medicine
Rinsho Shinkeigaku 46:890-2. 2006..These observations suggest that E4 is a rate-limiting factor in the degradation of proteins with expanded polyglutamine tracts...
Ligand-dependent transcription of estrogen receptor alpha is mediated by the ubiquitin ligase EFPAyako Nakajima
Department of Molecular Biochemistry, Hokkaido University Graduate School of Medicine, Kita ku, Sapporo, Hokkaido 060 8638, Japan
Biochem Biophys Res Commun 357:245-51. 2007..Our results indicate that EFP functions as a cofactor for ERalpha-mediated transcription, thus suggesting that ERalpha-mediated transcription is closely linked to the ubiquitylation of ERalpha...
APS-mediated ubiquitination of the insulin receptor enhances its internalization, but does not induce its degradationKazuhiro Kishi
Division of Molecular Genetics, Institute for Enzyme Research, The University of Tokushima, Japan
Endocr J 54:77-88. 2007..APS-mediated ubiquitination of the IR induced enhancement of the IR internalization, but did not affect the IR degradation. This finding shows one of the pleiotropic functions of APS in insulin signaling...
Elmo1 inhibits ubiquitylation of Dock180Yoshinori Makino
Laboratory of Molecular and Cellular Pathology, Hokkaido University Graduate School of Medicine, N15, W7, Sapporo 060 8638, Japan
J Cell Sci 119:923-32. 2006..Therefore, an ubiquitin-proteasome-dependent protein degradation mechanism might contribute to the local activation of Rac on the plasma membrane...
Mapping of ubiquitination sites on target proteinsShigetsugu Hatakeyama
Department of Molecular Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Japan
Methods Enzymol 399:277-86. 2005..Using these techniques, we can obtain comprehensive information about ubiquitinated proteins in various cells and tissues...
AIRE functions as an E3 ubiquitin ligaseDaisuke Uchida
Division of Molecular Immunology, Institute for Enzyme Research, University of Tokushima, 3 18 15 Kuramoto, Tokushima 770 8503, Japan
J Exp Med 199:167-72. 2004..These results add a novel enzymatic function for AIRE and suggest an indispensable role of the Ub proteasome pathway in the establishment of self-tolerance, in which AIRE is involved...
