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  • Humans  (3)
  • Cosmic Dust  (2)
  • 2005-2009  (5)
  • 1945-1949
  • 1
    Publication Date: 2009-07-22
    Description: Acquired uniparental disomy (aUPD) is a common feature of cancer genomes, leading to loss of heterozygosity. aUPD is associated not only with loss-of-function mutations of tumour suppressor genes, but also with gain-of-function mutations of proto-oncogenes. Here we show unique gain-of-function mutations of the C-CBL (also known as CBL) tumour suppressor that are tightly associated with aUPD of the 11q arm in myeloid neoplasms showing myeloproliferative features. The C-CBL proto-oncogene, a cellular homologue of v-Cbl, encodes an E3 ubiquitin ligase and negatively regulates signal transduction of tyrosine kinases. Homozygous C-CBL mutations were found in most 11q-aUPD-positive myeloid malignancies. Although the C-CBL mutations were oncogenic in NIH3T3 cells, c-Cbl was shown to functionally and genetically act as a tumour suppressor. C-CBL mutants did not have E3 ubiquitin ligase activity, but inhibited that of wild-type C-CBL and CBL-B (also known as CBLB), leading to prolonged activation of tyrosine kinases after cytokine stimulation. c-Cbl(-/-) haematopoietic stem/progenitor cells (HSPCs) showed enhanced sensitivity to a variety of cytokines compared to c-Cbl(+/+) HSPCs, and transduction of C-CBL mutants into c-Cbl(-/-) HSPCs further augmented their sensitivities to a broader spectrum of cytokines, including stem-cell factor (SCF, also known as KITLG), thrombopoietin (TPO, also known as THPO), IL3 and FLT3 ligand (FLT3LG), indicating the presence of a gain-of-function that could not be attributed to a simple loss-of-function. The gain-of-function effects of C-CBL mutants on cytokine sensitivity of HSPCs largely disappeared in a c-Cbl(+/+) background or by co-transduction of wild-type C-CBL, which suggests the pathogenic importance of loss of wild-type C-CBL alleles found in most cases of C-CBL-mutated myeloid neoplasms. Our findings provide a new insight into a role of gain-of-function mutations of a tumour suppressor associated with aUPD in the pathogenesis of some myeloid cancer subsets.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sanada, Masashi -- Suzuki, Takahiro -- Shih, Lee-Yung -- Otsu, Makoto -- Kato, Motohiro -- Yamazaki, Satoshi -- Tamura, Azusa -- Honda, Hiroaki -- Sakata-Yanagimoto, Mamiko -- Kumano, Keiki -- Oda, Hideaki -- Yamagata, Tetsuya -- Takita, Junko -- Gotoh, Noriko -- Nakazaki, Kumi -- Kawamata, Norihiko -- Onodera, Masafumi -- Nobuyoshi, Masaharu -- Hayashi, Yasuhide -- Harada, Hiroshi -- Kurokawa, Mineo -- Chiba, Shigeru -- Mori, Hiraku -- Ozawa, Keiya -- Omine, Mitsuhiro -- Hirai, Hisamaru -- Nakauchi, Hiromitsu -- Koeffler, H Phillip -- Ogawa, Seishi -- 2R01CA026038-30/CA/NCI NIH HHS/ -- England -- Nature. 2009 Aug 13;460(7257):904-8. doi: 10.1038/nature08240. Epub 2009 Jul 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Genomics Project, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19620960" target="_blank"〉PubMed〈/a〉
    Keywords: Allelic Imbalance ; Amino Acid Sequence ; Animals ; Base Sequence ; Chromosomes, Human, Pair 11/genetics ; Female ; *Genes, Tumor Suppressor ; Humans ; Leukemia, Myeloid/*genetics/metabolism/pathology ; Male ; Mice ; Mice, Knockout ; Mice, Nude ; Models, Molecular ; Molecular Sequence Data ; Mutant Proteins/chemistry/genetics/*metabolism ; Mutation ; NIH 3T3 Cells ; Neoplasm Transplantation ; Oncogenes/genetics ; Phosphorylation ; Protein Conformation ; Proto-Oncogene Proteins c-cbl/antagonists & ; inhibitors/chemistry/deficiency/*genetics/*metabolism ; Ubiquitination ; Uniparental Disomy/genetics ; ras Proteins/genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2007-01-27
    Description: Vitamin A has diverse biological functions. It is transported in the blood as a complex with retinol binding protein (RBP), but the molecular mechanism by which vitamin A is absorbed by cells from the vitamin A-RBP complex is not clearly understood. We identified in bovine retinal pigment epithelium cells STRA6, a multitransmembrane domain protein, as a specific membrane receptor for RBP. STRA6 binds to RBP with high affinity and has robust vitamin A uptake activity from the vitamin A-RBP complex. It is widely expressed in embryonic development and in adult organ systems. The RBP receptor represents a major physiological mediator of cellular vitamin A uptake.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kawaguchi, Riki -- Yu, Jiamei -- Honda, Jane -- Hu, Jane -- Whitelegge, Julian -- Ping, Peipei -- Wiita, Patrick -- Bok, Dean -- Sun, Hui -- 5T32EY07026/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 2007 Feb 9;315(5813):820-5. Epub 2007 Jan 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, David Geffen School of Medicine at UCLA, 650 Charles E. Young Drive South, Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17255476" target="_blank"〉PubMed〈/a〉
    Keywords: Acyltransferases/metabolism ; Amino Acid Sequence ; Animals ; Blood-Retinal Barrier ; COS Cells ; Cattle ; Cell Line ; Cell Line, Tumor ; Cell Membrane/metabolism ; Cercopithecus aethiops ; Embryonic Development ; Endocytosis ; Humans ; Molecular Sequence Data ; Mutation, Missense ; Pigment Epithelium of Eye/*metabolism ; Placenta/metabolism ; Receptors, Cell Surface/*metabolism ; Retinal Vessels/metabolism ; Retinol-Binding Proteins/*metabolism ; Spleen/metabolism ; Transfection ; Vitamin A/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2005-09-10
    Description: On 4 July 2005, many observatories around the world and in space observed the collision of Deep Impact with comet 9P/Tempel 1 or its aftermath. This was an unprecedented coordinated observational campaign. These data show that (i) there was new material after impact that was compositionally different from that seen before impact; (ii) the ratio of dust mass to gas mass in the ejecta was much larger than before impact; (iii) the new activity did not last more than a few days, and by 9 July the comet's behavior was indistinguishable from its pre-impact behavior; and (iv) there were interesting transient phenomena that may be correlated with cratering physics.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meech, K J -- Ageorges, N -- A'Hearn, M F -- Arpigny, C -- Ates, A -- Aycock, J -- Bagnulo, S -- Bailey, J -- Barber, R -- Barrera, L -- Barrena, R -- Bauer, J M -- Belton, M J S -- Bensch, F -- Bhattacharya, B -- Biver, N -- Blake, G -- Bockelee-Morvan, D -- Boehnhardt, H -- Bonev, B P -- Bonev, T -- Buie, M W -- Burton, M G -- Butner, H M -- Cabanac, R -- Campbell, R -- Campins, H -- Capria, M T -- Carroll, T -- Chaffee, F -- Charnley, S B -- Cleis, R -- Coates, A -- Cochran, A -- Colom, P -- Conrad, A -- Coulson, I M -- Crovisier, J -- deBuizer, J -- Dekany, R -- de Leon, J -- Dello Russo, N -- Delsanti, A -- DiSanti, M -- Drummond, J -- Dundon, L -- Etzel, P B -- Farnham, T L -- Feldman, P -- Fernandez, Y R -- Filipovic, M D -- Fisher, S -- Fitzsimmons, A -- Fong, D -- Fugate, R -- Fujiwara, H -- Fujiyoshi, T -- Furusho, R -- Fuse, T -- Gibb, E -- Groussin, O -- Gulkis, S -- Gurwell, M -- Hadamcik, E -- Hainaut, O -- Harker, D -- Harrington, D -- Harwit, M -- Hasegawa, S -- Hergenrother, C W -- Hirst, P -- Hodapp, K -- Honda, M -- Howell, E S -- Hutsemekers, D -- Iono, D -- Ip, W-H -- Jackson, W -- Jehin, E -- Jiang, Z J -- Jones, G H -- Jones, P A -- Kadono, T -- Kamath, U W -- Kaufl, H U -- Kasuga, T -- Kawakita, H -- Kelley, M S -- Kerber, F -- Kidger, M -- Kinoshita, D -- Knight, M -- Lara, L -- Larson, S M -- Lederer, S -- Lee, C-F -- Levasseur-Regourd, A C -- Li, J Y -- Li, Q-S -- Licandro, J -- Lin, Z-Y -- Lisse, C M -- LoCurto, G -- Lovell, A J -- Lowry, S C -- Lyke, J -- Lynch, D -- Ma, J -- Magee-Sauer, K -- Maheswar, G -- Manfroid, J -- Marco, O -- Martin, P -- Melnick, G -- Miller, S -- Miyata, T -- Moriarty-Schieven, G H -- Moskovitz, N -- Mueller, B E A -- Mumma, M J -- Muneer, S -- Neufeld, D A -- Ootsubo, T -- Osip, D -- Pandea, S K -- Pantin, E -- Paterno-Mahler, R -- Patten, B -- Penprase, B E -- Peck, A -- Petitas, G -- Pinilla-Alonso, N -- Pittichova, J -- Pompei, E -- Prabhu, T P -- Qi, C -- Rao, R -- Rauer, H -- Reitsema, H -- Rodgers, S D -- Rodriguez, P -- Ruane, R -- Ruch, G -- Rujopakarn, W -- Sahu, D K -- Sako, S -- Sakon, I -- Samarasinha, N -- Sarkissian, J M -- Saviane, I -- Schirmer, M -- Schultz, P -- Schulz, R -- Seitzer, P -- Sekiguchi, T -- Selman, F -- Serra-Ricart, M -- Sharp, R -- Snell, R L -- Snodgrass, C -- Stallard, T -- Stecklein, G -- Sterken, C -- Stuwe, J A -- Sugita, S -- Sumner, M -- Suntzeff, N -- Swaters, R -- Takakuwa, S -- Takato, N -- Thomas-Osip, J -- Thompson, E -- Tokunaga, A T -- Tozzi, G P -- Tran, H -- Troy, M -- Trujillo, C -- Van Cleve, J -- Vasundhara, R -- Vazquez, R -- Vilas, F -- Villanueva, G -- von Braun, K -- Vora, P -- Wainscoat, R J -- Walsh, K -- Watanabe, J -- Weaver, H A -- Weaver, W -- Weiler, M -- Weissman, P R -- Welsh, W F -- Wilner, D -- Wolk, S -- Womack, M -- Wooden, D -- Woodney, L M -- Woodward, C -- Wu, Z-Y -- Wu, J-H -- Yamashita, T -- Yang, B -- Yang, Y-B -- Yokogawa, S -- Zook, A C -- Zauderer, A -- Zhao, X -- Zhou, X -- Zucconi, J-M -- New York, N.Y. -- Science. 2005 Oct 14;310(5746):265-9. Epub 2005 Sep 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Astronomy, University of Hawaii at Manoa, 2680 Woodlawn Drive, Honolulu, HI 96822, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16150977" target="_blank"〉PubMed〈/a〉
    Keywords: Cosmic Dust ; Jupiter ; *Meteoroids ; Organic Chemicals ; Photometry
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2005-09-17
    Description: The impact cratering process on a comet is controversial but holds the key for interpreting observations of the Deep Impact collision with comet 9P/Tempel 1. Mid-infrared data from the Cooled Mid-Infrared Camera and Spectrometer (COMICS) of the Subaru Telescope indicate that the large-scale dust plume ejected by the impact contained a large mass (approximately 10(6) kilograms) of dust and formed two wings approximately +/-45 degrees from the symmetric center, both consistent with gravity as the primary control on the impact and its immediate aftermath. The dust distribution in the inner part of the plume, however, is inconsistent with a pure gravity control and implies that evaporation and expansion of volatiles accelerated dust.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sugita, S -- Ootsubo, T -- Kadono, T -- Honda, M -- Sako, S -- Miyata, T -- Sakon, I -- Yamashita, T -- Kawakita, H -- Fujiwara, H -- Fujiyoshi, T -- Takato, N -- Fuse, T -- Watanabe, J -- Furusho, R -- Hasegawa, S -- Kasuga, T -- Sekiguchi, T -- Kinoshita, D -- Meech, K J -- Wooden, D H -- Ip, W H -- A'Hearn, M F -- New York, N.Y. -- Science. 2005 Oct 14;310(5746):274-8. Epub 2005 Sep 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Complexity Science and Engineering, University of Tokyo, Kashiwa, Chiba, Japan. sugita@k.u-tokyo.ac.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16166476" target="_blank"〉PubMed〈/a〉
    Keywords: Cosmic Dust ; Jupiter ; *Meteoroids ; Spectrophotometry, Infrared ; Volatilization
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2009-12-08
    Description: Bub1 is a multi-task protein kinase required for proper chromosome segregation in eukaryotes. Impairment of Bub1 in humans may lead to chromosomal instability (CIN) or tumorigenesis. Yet, the primary cellular substrate of Bub1 has remained elusive. Here, we show that Bub1 phosphorylates the conserved serine 121 of histone H2A in fission yeast Schizosaccharomyces pombe. The h2a-SA mutant, in which all cellular H2A-S121 is replaced by alanine, phenocopies the bub1 kinase-dead mutant (bub1-KD) in losing the centromeric localization of shugoshin proteins. Artificial tethering of shugoshin to centromeres largely restores the h2a-SA or bub1-KD-related CIN defects, a function that is evolutionally conserved. Thus, Bub1 kinase creates a mark for shugoshin localization and the correct partitioning of chromosomes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kawashima, Shigehiro A -- Yamagishi, Yuya -- Honda, Takashi -- Ishiguro, Kei-ichiro -- Watanabe, Yoshinori -- New York, N.Y. -- Science. 2010 Jan 8;327(5962):172-7. doi: 10.1126/science.1180189. Epub 2009 Nov 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Tokyo 113-0032, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965387" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Centromere/*metabolism ; *Chromosomal Instability ; Chromosomal Proteins, Non-Histone/genetics/*metabolism ; *Chromosome Segregation ; Chromosomes, Fungal/metabolism ; Histones/*metabolism ; Humans ; Kinetochores/metabolism ; Meiosis ; Mice ; Mitosis ; Nucleosomes/metabolism ; Phosphorylation ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; Recombinant Proteins/metabolism ; Saccharomyces cerevisiae/genetics/metabolism ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; Schizosaccharomyces/cytology/genetics/*metabolism ; Schizosaccharomyces pombe Proteins/genetics/*metabolism ; Serine/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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