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Interaction of anti‐proliferative protein Tob with poly(A)‐binding protein and inducible poly(A)‐binding protein: implication of Tob in translational control
Author(s) -
Okochi Kentaro,
Suzuki Toru,
Inoue Junichiro,
Matsuda Satoru,
Yamamoto Tadashi
Publication year - 2005
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2005.00826.x
Subject(s) - biology , poly(a) binding protein , binding protein , plasma protein binding , microbiology and biotechnology , biochemistry , messenger rna , rna binding protein , gene
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.