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Publication : IAN family critically regulates survival and development of T lymphocytes.

First Author  Nitta T Year  2006
Journal  PLoS Biol Volume  4
Issue  4 Pages  e103
PubMed ID  16509771 Mgi Jnum  J:107746
Mgi Id  MGI:3621847 Doi  10.1371/journal.pbio.0040103
Citation  Nitta T, et al. (2006) IAN family critically regulates survival and development of T lymphocytes. PLoS Biol 4(4):e103
abstractText  The IAN (immune-associated nucleotide-binding protein) family is a family of functionally uncharacterized GTP-binding proteins expressed in vertebrate immune cells and in plant cells during antibacterial responses. Here we show that all eight IAN family genes encoded in a single cluster of mouse genome are predominantly expressed in lymphocytes, and that the expression of IAN1, IAN4, and IAN5 is significantly elevated upon thymic selection of T lymphocytes. Gain-of-function experiments show that the premature overexpression of IAN1 kills immature thymocytes, whereas short hairpin RNA-mediated loss-of-function studies show that IAN4 supports positive selection. The knockdown of IAN5 perturbs the optimal generation of CD4/CD8 double-positive thymocytes and reduces the survival of mature T lymphocytes. We also show evidence suggesting that IAN4 and IAN5 are associated with anti-apoptotic proteins Bcl-2 and Bcl-xL, whereas IAN1 is associated with pro-apoptotic Bax. Thus, the IAN family is a novel family of T cell-receptor-responsive proteins that critically regulate thymic development and survival of T lymphocytes and that potentially exert regulatory functions through the association with Bcl-2 family proteins.
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