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1 Divisions of Oncology
2 Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
3 Department of Life Science and Human Technology, Nara Women's University, Kita-Uoya Nishimachi, Nara 630-8506, Japan
4 Depertment of Molecular Medicine, Faculty of Medicine, Osaka University, 2-2 Yamadaoka, Suita-shi, Osaka 565-0871, Japan
Tob is a member of an emerging family of anti-proliferative proteins that suppress cell growth when over-expressed. tob mRNA is highly expressed in anergic T cells and over-expression of Tob suppresses transcription of interleukin-2 (IL-2) through its interaction with Smads. Here, we identified two types of cDNA clones coding for poly(A)-binding protein (PABP) and inducible PABP (iPABP) by screening an expression cDNA library with the GST-Tob probe. Co-immunoprecipitation and GST-pull down experiments showed that Tob associated with the carboxyl-terminal region of iPABP. We then found that iPABP, like PABP, was involved in regulation of translation: iPABP enhanced translation of IL-2 mRNA in vitro. The enhanced translation of IL-2 mRNA required the 3'UTR and poly(A) sequences. Tob abrogated the enhancement of translation through its interaction with carboxyl-terminal region of iPABP in vitro. Consistently, over-expression of Tob in NIH3T3 cells, in which exogenous iPABP was stably expressed, resulted in suppression of IL-2 production from the simultaneously transfected IL-2 expression plasmid. Finally, Tob, whose expression was induced by anergic stimulation, was co-immunoprecipitated with iPABP in human T cells. These findings suggest that Tob is involved in the translational suppression of IL-2 mRNA in anergic T cells through its interaction with iPABP.
* Correspondence: E-mail: tyamamot{at}ims.u-tokyo.ac.jp
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