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  • 1
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    NUMB controls p53 tumour suppressor activity (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-01-04
    Description: NUMB is a cell fate determinant, which, by asymmetrically partitioning at mitosis, controls cell fate choices by antagonising the activity of the plasma membrane receptor of the NOTCH family. NUMB is also an endocytic protein, and the NOTCH-NUMB counteraction has been linked to this function. There might be, however, additional functions of NUMB, as witnessed by its proposed role as a tumour suppressor in breast cancer. Here we describe a previously unknown function for human NUMB as a regulator of tumour protein p53 (also known as TP53). NUMB enters in a tricomplex with p53 and the E3 ubiquitin ligase HDM2 (also known as MDM2), thereby preventing ubiquitination and degradation of p53. This results in increased p53 protein levels and activity, and in regulation of p53-dependent phenotypes. In breast cancers there is frequent loss of NUMB expression. We show that, in primary breast tumour cells, this event causes decreased p53 levels and increased chemoresistance. In breast cancers, loss of NUMB expression causes increased activity of the receptor NOTCH. Thus, in these cancers, a single event-loss of NUMB expression-determines activation of an oncogene (NOTCH) and attenuation of the p53 tumour suppressor pathway. Biologically, this results in an aggressive tumour phenotype, as witnessed by findings that NUMB-defective breast tumours display poor prognosis. Our results uncover a previously unknown tumour suppressor circuitry.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Colaluca, Ivan N -- Tosoni, Daniela -- Nuciforo, Paolo -- Senic-Matuglia, Francesca -- Galimberti, Viviana -- Viale, Giuseppe -- Pece, Salvatore -- Di Fiore, Pier Paolo -- England -- Nature. 2008 Jan 3;451(7174):76-80. doi: 10.1038/nature06412.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉IFOM, the FIRC Institute for Molecular Oncology Foundation, Via Adamello 16, 20139, Milan, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18172499" target="_blank"〉PubMed〈/a〉
    Keywords: Breast Neoplasms/genetics/metabolism/pathology ; Cell Line, Tumor ; Cells, Cultured ; DNA Damage ; Drug Resistance, Neoplasm ; Gene Silencing ; Humans ; Membrane Proteins/deficiency/genetics/*metabolism ; Nerve Tissue Proteins/deficiency/genetics/*metabolism ; Prognosis ; Protein Binding ; Proto-Oncogene Proteins c-mdm2/metabolism ; Tumor Suppressor Protein p53/*metabolism ; Ubiquitination
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    A gut-vascular barrier controls the systemic dissemination of bacteria (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-11-14
    Description: In healthy individuals, the intestinal microbiota cannot access the liver, spleen, or other peripheral tissues. Some pathogenic bacteria can reach these sites, however, and can induce a systemic immune response. How such compartmentalization is achieved is unknown. We identify a gut-vascular barrier (GVB) in mice and humans that controls the translocation of antigens into the blood stream and prohibits entry of the microbiota. Salmonella typhimurium can penetrate the GVB in a manner dependent on its pathogenicity island (Spi) 2-encoded type III secretion system and on decreased beta-catenin-dependent signaling in gut endothelial cells. The GVB is modified in celiac disease patients with elevated serum transaminases, which indicates that GVB dismantling may be responsible for liver damage in these patients. Understanding the GVB may provide new insights into the regulation of the gut-liver axis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Spadoni, Ilaria -- Zagato, Elena -- Bertocchi, Alice -- Paolinelli, Roberta -- Hot, Edina -- Di Sabatino, Antonio -- Caprioli, Flavio -- Bottiglieri, Luca -- Oldani, Amanda -- Viale, Giuseppe -- Penna, Giuseppe -- Dejana, Elisabetta -- Rescigno, Maria -- New York, N.Y. -- Science. 2015 Nov 13;350(6262):830-4. doi: 10.1126/science.aad0135.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Experimental Oncology, European Institute of Oncology, Milan, Italy. ; The Italian Foundation for Cancer Research (FIRC) Institute of Molecular Oncology (IFOM), Milan, Italy. ; First Department of Medicine, St. Matteo Hospital, University of Pavia, Pavia, Italy. ; Unita Operativa Gastroenterologia ed Endoscopia, Fondazione IRCCS Ca Granda, Ospedale Maggiore Policlinico di Milano, and Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Universita degli Studi di Milano, Milan, Italy. ; Department of Pathology and Laboratory Medicine, European Institute of Oncology, Milan, Italy. ; The Italian Foundation for Cancer Research (FIRC) Institute of Molecular Oncology (IFOM), Milan, Italy. Department of Biosciences, Universita degli Studi di Milano, Italy. Department of Genetics, Immunology and Pathology, Uppsala University, Uppsala, Sweden. ; Department of Experimental Oncology, European Institute of Oncology, Milan, Italy. Department of Biosciences, Universita degli Studi di Milano, Italy. maria.rescigno@ieo.eu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26564856" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Bacterial/blood/immunology ; Capillary Permeability/*immunology ; Celiac Disease/blood/immunology/microbiology ; Genomic Islands/genetics/immunology ; Humans ; Ileum/blood supply/immunology/microbiology ; Intestinal Mucosa/immunology/microbiology ; Intestines/blood supply/*immunology/*microbiology ; Liver/immunology ; Mice ; Mice, Inbred C57BL ; Microbiota/*immunology ; Salmonella Infections/*immunology ; Salmonella typhimurium/genetics/*immunology/pathogenicity ; Signal Transduction ; Spleen/immunology ; Transaminases/blood ; Type III Secretion Systems/genetics/immunology ; Wnt Signaling Pathway ; beta Catenin/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
    Electronic Resource
    Electronic Resource
    Origin and function of tomato bushy stunt virus-induced inclusion bodies
    Amsterdam : Elsevier
    Journal of Ultrastructure Research and Molecular Structure Research 97 (1986), S. 31-38 
    Details
    ISSN: 0889-1605
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1016/S0889-1605(86)80004-0
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  • 4
    Electronic Resource
    Electronic Resource
    Origin and function of tomato bushy stunt virus-induced inclusion bodies
    Amsterdam : Elsevier
    Journal of Ultrastructure Research and Molecular Structure Research 97 (1986), S. 31-38 
    Details
    ISSN: 0889-1605
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1016/S0889-1605(86)80004-0
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  • 5
    Electronic Resource
    Electronic Resource
    Preparation and characterization of anti-human chromogranin A and chromogranin B (secretogranin I) monoclonal antibodies
    Amsterdam : Elsevier
    Molecular and Cellular Probes 3 (1989), S. 87-101 
    Details
    ISSN: 0890-8508
    Keywords: chromaffin granules ; chromogranins ; immunocytochemistry ; pheochromocytoma ; two-dimensional immunoblotting
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1016/0890-8508(89)90039-X
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  • 6
    Electronic Resource
    Electronic Resource
    Microvasculature involvement in some connective tissue disorders: An immuno-histochemical and ultrastructural approach
    Amsterdam : Elsevier
    Ultramicroscopy 12 (1983), S. 152 
    Details
    ISSN: 0304-3991
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Electrical Engineering, Measurement and Control Technology , Natural Sciences in General , Physics
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0304-3991(83)90433-3
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  • 7
    Electronic Resource
    Electronic Resource
    Ultrastructural localization of extracellular immunoglobulins in immune-complex-mediated glomerulonephritis (1986)
    Springer
    Histochemistry and cell biology 84 (1986), S. 1-4 
    Details
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The ultrastructural localization of immunoglobulins (Igs) in immunologically mediated glomerulonephritis was achieved in ultrathin sections of glutaraldehyde-fixed, post-osmicated, Epon-embedded human renal needle biopsies using the indirect immunogold staining procedure. Extracellular Igs were identified in electron-dense deposits in subendothelia, intramembranous, subepithelial and mesangial locations in different cases of immune-complex-mediated glomerulonephritis. The excellent preservation of the ultrastructural morphology of the tissue sections made it possible to precisely correlate the presence and distribution of the antigens with those of the electron-dense deposits, which are the ultrastructural hallmarks of these diseases. Our post-embedding staining procedure which allows extracellular Igs to be accurately localized should be a very useful tool for immunomorphological investigations of glomerulo-nephritis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00493411
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  • 8
    Electronic Resource
    Electronic Resource
    Differences in the organization and chromosomal allocation of satellite DNA between the European long tailed house miceMus domesticus andMus musculus (1990)
    Springer
    Chromosoma 99 (1990), S. 11-17 
    Details
    ISSN: 1432-0886
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We compared the organization of satellite DNA (stDNA) and its chromosomal allocation inMus domesticus and inMus musculus. The two stDNAs show similar restriction fragment profiles after digestion (probed withM. domesticus stDNA) with some endonucleases of which restriction sequences are present in the 230–240 bp repetitive unit of theM. domesticus stDNA. In contrast, EcoRI digestion reveals thatM. musculus stDNA lacks most of the GAATTC restriction sites, particularly at the level of the half-monomer. The chromosome distribution of stDNA (revealed by anM. domesticus stDNA probe) shows different patterns in theM. domesticus andM. musculus karyotypes, with about 60% ofM. domesticus stDNA retained in theM. musculus genome. It is particularly noteworthy that the pericentromeric regions ofM. musculus chromosomes 1 and X are totally devoid ofM. domesticus stDNA sequences. In both groups, the differences in energy transfer between the stDNA-bound fluorochromes Hoechst 33258 and propidium iodide suggest that AT-rich repeated sequences have a much more clustered array in theM. domesticus stDNA, as if they are organized in tandem repeats longer than those ofM. musculus. Considering the data as a whole, it seems likely that the evolutionary paths of the two stDNAs diverged after the generation of the ancestral 230–240 bp stDNA repetitive unit through the amplification, in theM. domesticus genome, of a family repeat which included the EcoRI GAATTC restriction sequence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01737284
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  • 9
    Electronic Resource
    Electronic Resource
    Über die Anwendung von Nicotinsäureamid beim histochemischen Nachweis pyridinnucleotidgebundener Enzyme im Hirngewebe (1961)
    Springer
    Histochemistry and cell biology 2 (1961), S. 322-331 
    Details
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00848036
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  • 10
    Electronic Resource
    Electronic Resource
    Extracellular matrix proteins, integrin receptors (VLA-β1, VLA-α2 and VLA-α5) and growth fraction in atypical macroregenerative nodules of the liver: an immunocytochemical case study (1994)
    Springer
    Histochemistry and cell biology 102 (1994), S. 29-36 
    Details
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract A case of cirrhotic liver harbouring three atypical macroregenerative nodules and an hepatocellular carcinoma was immunocytochemically investigated for the expression of VLA-β 1, VLA-α2 and VLA-α5 integrins and for different extracellular matrix (ECM) components (collagen I, collagen IV, laminin, fibronectin and tenascin). In addition, the proliferative activity within the nodules was evaluated, using the MIB 1 monoclonal antibody (MAb). The cirrhotic liver disclosed a continuous staining pattern of the ECM proteins investigated, as well as a “sinusoidal” immunostaining of VLA-β1, VLA-α2 and VLA-α5. The macroregenerative nodules showed a discontinued immunoreactivity for ECM proteins while maintaining a VLA-β1 sinusoidal immunostaining, coupled with intercellular immunostaining. VLA-α2 and VLA-α5 expression was lacking. The growth fraction was low in both the above pathological conditions. The hepatocellular carcinoma was devoid of any ECM immunostaining. VLA-β1 immunoreactivity exhibited a honeycomb pattern of staining, whereas VLA α subunits were absent. MIB1 expression was high, being present in 30% of neoplastic nuclei. A possible relationship between atypical macroregenerative nodules and hepatocellular carcinoma is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00271046
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