Transforming growth factor-b (TGF-b) receptors (TbRs) are essential components for TGF-b signal transduction in T cells, yet the mechanisms by which the receptors are regulated remain poorly understood. We show here that Poly(ADP-ribose) polymerase-1 (PARP-1) regulates TGF-b receptor I (TbRI) and II (TbRII) expression in CD4+ T cells and subsequently affects Smad2/3-mediated TGF-b signal transduction. Inhibition of PARP-1 led to the upregulation of both TbRI and TbRII, yet the underlying molecular mechanisms were distinct. PARP-1 selectively bound to the promoter of TbRII, whereas the enzymatic activity of PARP-1 was responsible for the inhibition of TbRI expression. Importantly, inhibition of PARP-1 also enhanced expression of TbRs in human CD4+ T cells. Thus, PARP-1 regulates TbR expression and TGF-b signaling in T cells.
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