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The Journal of Immunology, 1999, 163: 1888-1893.
Copyright © 1999 by The American Association of Immunologists

In Vivo Overexpression of Dad1, the Defender Against Apoptotic Death-1, Enhances T Cell Proliferation But Does Not Protect Against Apoptosis1

N. A. Hong2, N. H. Kabra, S. N. Hsieh, D. Cado and A. Winoto3

Division of Immunology and Cancer Research Laboratory, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720

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.




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