IAN family critically regulates survival and development of T lymphocytes.
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.
Nitta
Takeshi
T
Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Tokushima, Japan.
Nasreen
Mariam
M
Seike
Takafumi
T
Goji
Atsushi
A
Ohigashi
Izumi
I
Miyazaki
Tadaaki
T
Ohta
Tsutomu
T
Kanno
Masamoto
M
Takahama
Yousuke
Y
D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002470:Cell Survival; D019204:GTP-Binding Proteins / Q000145:classification* / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D016678:Genome / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034622:RNA Interference; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism
D019253:Proto-Oncogene Proteins c-bcl-2; D019204:GTP-Binding Proteins