Mucosal Immunology Section, Oral Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD;
Blood. 2013 Sep 26;122(13):2224-32. doi: 10.1182/blood-2013-05-503250. Epub 2013 Aug 12.
Transforming growth factor-β (TGF-β) receptors (TβRs) are essential components for TGF-β 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-β receptor I (TβRI) and II (TβRII) expression in CD4(+) T cells and subsequently affects Smad2/3-mediated TGF-β signal transduction. Inhibition of PARP-1 led to the upregulation of both TβRI and TβRII, yet the underlying molecular mechanisms were distinct. PARP-1 selectively bound to the promoter of TβRII, whereas the enzymatic activity of PARP-1 was responsible for the inhibition of TβRI expression. Importantly, inhibition of PARP-1 also enhanced expression of TβRs in human CD4(+) T cells. Thus, PARP-1 regulates TβR expression and TGF-β signaling in T cells.
转化生长因子-β（TGF-β）受体（TβRs）是 T 细胞中 TGF-β信号转导的重要组成部分，但受体的调节机制仍知之甚少。我们在这里表明，多聚（ADP-核糖）聚合酶-1（PARP-1）在 CD4+T 细胞中调节 TGF-β受体 I（TβRI）和 II（TβRII）的表达，随后影响 Smad2/3 介导的 TGF-β信号转导。PARP-1 的抑制导致 TβRI 和 TβRII 的上调，但潜在的分子机制是不同的。PARP-1 选择性地结合于 TβRII 的启动子，而 PARP-1 的酶活性负责抑制 TβRI 的表达。重要的是，PARP-1 的抑制也增强了人 CD4+T 细胞中 TβRs 的表达。因此，PARP-1 调节 T 细胞中 TβR 的表达和 TGF-β 信号转导。
