PARP-1 regulates expression of TGF-ß receptors in T cells.

ABSTRACT

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