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. Author manuscript; available in PMC: 2015 Jun 1.
Published in final edited form as: Clin Exp Neuroimmunol. 2014 Jun 26;5(2):132–136. doi: 10.1111/cen3.12125

Figure. Tob1 in T cells.

Figure

Tob1 gets downregulated following TCR signaling. In the nucleus Tob1 enhances binding of Smad4 to the negative cis regulatory element (CRE) of the IL-2 gene, thus negatively affecting IL2 expression. Concomitantly, the stability of IL2 mRNA is also regulated by the interaction of Tob1 and PABC and iPABC, a complex that favors deadenylation and subsequent mRNA decay. Through its interaction with CCR4 and Caf-1, Tob1 also inhibits IL2 mRNA translation. These coordinated actions by Tob1 result in quick IL2 downregulation and inhibition of cell division. In the cytoplasm, Tob1 also inhibits Tsg, which in turn, stimulates TGFb-mediated control of cell activation. TGFb acts through its heterodimeric receptor and phosphorylate Smad2 and Smad3, which when complexed with SMad4 translocate to the nucleus. Once there, Tob1 enhances Smad-mediated transcriptional activation of Dpp2 and p27, promoting T cell quiescence.