SEARCH:   Advanced

Blood, 15 May 2008, Vol. 111, No. 10, pp. 5017-5027. Prepublished online as a Blood First Edition Paper on March 11, 2008; DOI 10.1182/blood-2007-12-130856. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-12-130856v1 111/10/5017    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Finetti, F. Articles by Baldari, C. T Search for Related Content PubMed PubMed Citation Articles by Finetti, F. Articles by Baldari, C. T Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 27, 2007 Accepted March 7, 2008 The proapoptotic and antimitogenic protein p66SHC acts as a negative regulator of lymphocyte activation and autoimmunity Francesca Finetti, Michela Pellegrini, Cristina Ulivieri, Maria Teresa Savino, Eugenio Paccagnini, Chiara Ginanneschi, Luisa Lanfrancone, Pier Giuseppe Pelicci, and Cosima T Baldari* Department of Evolutionary Biology, University of Siena, Siena, Italy Department of Human Pathology and Oncology, Policlinico Le Scotte, University of Siena, Siena, Italy Department of Molecular Oncology, European Institute of Oncology, Milan, Italy * Corresponding author; email: baldari{at}unisi.it. The ShcA locus encodes three protein isoforms which differ in tissue specificity, subcellular localization and function. Among these, p66Shc inhibits TCR coupling to the Ras/MAPK pathway and primes T cells to undergo apoptotic death. We have investigated the outcome of p66Shc deficiency on lymphocyte development and homeostasis. We show that p66Shc-/- mice develop an age-related lupus-like autoimmune disease characterized by spontaneous peripheral T- and B-cell activation and proliferation, autoantibody production and immune complex deposition in kidney and skin, resulting in autoimmune glomerulonephritis and alopecia. p66Shc-/- lymphocytes display enhanced proliferation in response to antigen receptor engagement in vitro and more robust immune responses both to vaccination and to allergen sensitization in vivo. The data identify p66Shc as a negative regulator of lymphocyte activation and show that loss of this protein results in breaking of immunological tolerance and development of systemic autoimmunity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Guo, Z. Gertsberg, N. Ozgen, and S. F. Steinberg p66Shc Links {alpha}1-Adrenergic Receptors to a Reactive Oxygen Species-Dependent AKT-FOXO3A Phosphorylation Pathway in Cardiomyocytes Circ. Res., March 13, 2009; 104(5): 660 - 669. [Abstract] [Full Text] [PDF] M. T. Savino, B. Ortensi, M. Ferro, C. Ulivieri, D. Fanigliulo, E. Paccagnini, S. Lazzi, D. Osti, G. Pelicci, and C. T. Baldari Rai Acts as a Negative Regulator of Autoimmunity by Inhibiting Antigen Receptor Signaling and Lymphocyte Activation J. Immunol., January 1, 2009; 182(1): 301 - 308. [Abstract] [Full Text] [PDF]

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020