IAN Family Critically Regulates Survival and Development of T Lymphocytes

Takeshi Nitta, Mariam Nasreen, Takafumi Seike, Atsushi Goji, Izumi Ohigashi, Tadaaki Miyazaki, Tsutomu Ohta, Masamoto Kanno, Yousuke Takahama, Philippa Marrack
2006 PLoS Biology  
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-offunction experiments show that
more » ... 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-receptorresponsive 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. Citation: Nitta T, Nasreen M, Seike T, Goji A, Ohigashi I, et al. (2006) IAN family critically regulates survival and development of t lymphocytes. PLoS Biol 4(4): e103.
doi:10.1371/journal.pbio.0040103 pmid:16509771 pmcid:PMC1393758 fatcat:byxh2kijrnd7zgqnmbjjhdnkda