PARP-1 regulates expression of TGF-β receptors in T cells

Transforming growth factor-beta (TGF-beta) receptors (T beta Rs) are essential components for TGF-beta 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-beta receptor I (T beta RI) and II (T beta RII) expression in CD4(+) T cells and subsequently affects Smad2/3-mediated TGF-beta signal transduction. Inhibition of PARP-1 led to the upregulation of both T beta RI and T beta RII, yet the underlying molecular mechanisms were distinct. PARP-1 selectively bound to the promoter of T beta RII, whereas the enzymatic activity of PARP-1 was responsible for the inhibition of T beta RI expression. Importantly, inhibition of PARP-1 also enhanced expression of T beta Rs in human CD4(+) T cells. Thus, PARP-1 regulates T beta R expression and TGF-beta signaling in T cells.