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Rap1 and SPA-1 in hematologic malignancy
Rap1 is a member of the Ras family of GTPases and, depending on the cellular context, has an important role in the regulation of proliferation or cell adhesion. In lymphohematopoietic tissues, SPA-1 is a principal Rap1 GTPase-activating protein. Mice that are deficient for the SPA-1 gene develop age...
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Published in: | Trends in molecular medicine 2004-08, Vol.10 (8), p.401-408 |
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creator | Kometani, Kohei Ishida, Daisuke Hattori, Masakazu Minato, Nagahiro |
description | Rap1 is a member of the Ras family of GTPases and, depending on the cellular context, has an important role in the regulation of proliferation or cell adhesion. In lymphohematopoietic tissues, SPA-1 is a principal Rap1 GTPase-activating protein. Mice that are deficient for the
SPA-1 gene develop age-dependent progression of T-cell immunodeficiency followed by a spectrum of late onset myeloproliferative disorders, mimicking human chronic myeloid leukemia. Recent studies reveal that deregulated Rap1 activation in SPA-1-deficient mice causes enhanced expansion of the bone marrow hematopoietic progenitors, but induces progressive unresponsiveness or anergy in T cells. Rap1 and its regulator, SPA-1, could, therefore, provide unique molecular targets for the control of human hematologic malignancy. |
doi_str_mv | 10.1016/j.molmed.2004.06.004 |
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SPA-1 gene develop age-dependent progression of T-cell immunodeficiency followed by a spectrum of late onset myeloproliferative disorders, mimicking human chronic myeloid leukemia. Recent studies reveal that deregulated Rap1 activation in SPA-1-deficient mice causes enhanced expansion of the bone marrow hematopoietic progenitors, but induces progressive unresponsiveness or anergy in T cells. Rap1 and its regulator, SPA-1, could, therefore, provide unique molecular targets for the control of human hematologic malignancy.</description><identifier>ISSN: 1471-4914</identifier><identifier>EISSN: 1471-499X</identifier><identifier>DOI: 10.1016/j.molmed.2004.06.004</identifier><identifier>PMID: 15310461</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; Clonal Anergy ; GTPase-Activating Proteins - genetics ; GTPase-Activating Proteins - physiology ; Hematologic Neoplasms - genetics ; Hematologic Neoplasms - metabolism ; Hematologic Neoplasms - prevention & control ; Humans ; Mice ; Mice, Knockout ; Nuclear Proteins - genetics ; Nuclear Proteins - physiology ; rap1 GTP-Binding Proteins - metabolism ; T-Lymphocytes - immunology</subject><ispartof>Trends in molecular medicine, 2004-08, Vol.10 (8), p.401-408</ispartof><rights>2004 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c389t-189a3bd85a24bec471a0f1253437d2ca9eed8bd392babd4cd8363ef23a9471083</citedby><cites>FETCH-LOGICAL-c389t-189a3bd85a24bec471a0f1253437d2ca9eed8bd392babd4cd8363ef23a9471083</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15310461$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kometani, Kohei</creatorcontrib><creatorcontrib>Ishida, Daisuke</creatorcontrib><creatorcontrib>Hattori, Masakazu</creatorcontrib><creatorcontrib>Minato, Nagahiro</creatorcontrib><title>Rap1 and SPA-1 in hematologic malignancy</title><title>Trends in molecular medicine</title><addtitle>Trends Mol Med</addtitle><description>Rap1 is a member of the Ras family of GTPases and, depending on the cellular context, has an important role in the regulation of proliferation or cell adhesion. In lymphohematopoietic tissues, SPA-1 is a principal Rap1 GTPase-activating protein. Mice that are deficient for the
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subjects | Animals Clonal Anergy GTPase-Activating Proteins - genetics GTPase-Activating Proteins - physiology Hematologic Neoplasms - genetics Hematologic Neoplasms - metabolism Hematologic Neoplasms - prevention & control Humans Mice Mice, Knockout Nuclear Proteins - genetics Nuclear Proteins - physiology rap1 GTP-Binding Proteins - metabolism T-Lymphocytes - immunology |
title | Rap1 and SPA-1 in hematologic malignancy |
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