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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Bibliographic Details
Published in:Trends in molecular medicine 2004-08, Vol.10 (8), p.401-408
Main Authors: Kometani, Kohei, Ishida, Daisuke, Hattori, Masakazu, Minato, Nagahiro
Format: Article
Language:English
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
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Summary: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.
ISSN:1471-4914
1471-499X
DOI:10.1016/j.molmed.2004.06.004