In Vivo Overexpression of Dad1, the Defender Against Apoptotic Death-1, Enhances T Cell Proliferation But Does Not Protect Against Apoptosis

The Dad1 protein has been shown to play a role in prevention of apoptosis in certain cell types. Dad1 is also a subunit of the oligosaccharyltransferase enzyme complex that initiates N-linked glycosylation. It is encoded by a gene located adjacent to the TCR alpha and delta genes on mouse chromosome...

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Bibliographic Details
Published in:The Journal of immunology (1950) 1999-08, Vol.163 (4), p.1888-1893
Main Authors: Hong, N. A, Kabra, N. H, Hsieh, S. N, Cado, D, Winoto, A
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - biosynthesis
Adjuvants, Immunologic - physiology
Animals
Apoptosis - genetics
Apoptosis - immunology
Apoptosis Regulatory Proteins
Cells, Cultured
Lymphocyte Activation - genetics
Lymphocyte Activation - immunology
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - genetics
Membrane Proteins - biosynthesis
Membrane Proteins - genetics
Membrane Proteins - physiology
Mice
Mice, Transgenic
Promoter Regions, Genetic - immunology
T-Lymphocytes - cytology
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
Thymus Gland - cytology
Thymus Gland - metabolism
Transgenes - immunology
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Summary:The Dad1 protein has been shown to play a role in prevention of apoptosis in certain cell types. Dad1 is also a subunit of the oligosaccharyltransferase enzyme complex that initiates N-linked glycosylation. It is encoded by a gene located adjacent to the TCR alpha and delta genes on mouse chromosome 14. We have investigated the role of Dad1 during T cell development and activation. We observe that endogenous Dad1 levels are modulated during T cell development to reach maximal expression in mature thymocytes. Transgenic mice that overexpress Dad1 in both the thymus and peripheral immune system have been generated. Apoptosis of thymocytes from such mice is largely unaffected, but peripheral T cells display hyperproliferation in response to stimuli. Therefore, the linkage between the TCR and Dad1 genes may have important consequences for T cell function.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.163.4.1888