PARP-1 调节 T 细胞中 TGF-β 受体的表达。
PARP-1 regulates expression of TGF-β receptors in T cells.
机构信息
Mucosal Immunology Section, Oral Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD;
出版信息
Blood. 2013 Sep 26;122(13):2224-32. doi: 10.1182/blood-2013-05-503250. Epub 2013 Aug 12.
Abstract
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.
摘要
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。
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本文引用的文献
1
Balancing acts: the role of TGF-β in the mucosal immune system.平衡之道：TGF-β 在黏膜免疫系统中的作用。
Trends Mol Med. 2011 Nov;17(11):668-76. doi: 10.1016/j.molmed.2011.07.002. Epub 2011 Sep 2.
2
Indoleamine 2,3-dioxygenase is a signaling protein in long-term tolerance by dendritic cells.吲哚胺 2,3-双加氧酶是树突状细胞长期耐受中的信号蛋白。
Nat Immunol. 2011 Jul 31;12(9):870-8. doi: 10.1038/ni.2077.
3
Control of the differentiation of regulatory T cells and T(H)17 cells by the DNA-binding inhibitor Id3.DNA 结合抑制因子 Id3 对调节性 T 细胞和 T(H)17 细胞分化的调控。
Nat Immunol. 2011 Jan;12(1):86-95. doi: 10.1038/ni.1965. Epub 2010 Dec 5.
4
PARP-1 attenuates Smad-mediated transcription.PARP-1 可减弱 Smad 介导的转录。
Mol Cell. 2010 Nov 24;40(4):521-32. doi: 10.1016/j.molcel.2010.10.029.
5
Generation of pathogenic T(H)17 cells in the absence of TGF-β signalling.在缺乏 TGF-β 信号的情况下生成致病性 T(H)17 细胞。
Nature. 2010 Oct 21;467(7318):967-71. doi: 10.1038/nature09447.
6
The PARP side of the nucleus: molecular actions, physiological outcomes, and clinical targets.核内的 PARP 侧：分子作用、生理结果和临床靶标。
Mol Cell. 2010 Jul 9;39(1):8-24. doi: 10.1016/j.molcel.2010.06.017.
7
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J Immunol. 2010 Jul 15;185(2):842-55. doi: 10.4049/jimmunol.0904100. Epub 2010 Jun 14.
8
Th17 and regulatory T cells in mediating and restraining inflammation.辅助性 T 细胞 17 和调节性 T 细胞在炎症的介导和抑制中的作用。
Cell. 2010 Mar 19;140(6):845-58. doi: 10.1016/j.cell.2010.02.021.
9
Increased Foxp3+ regulatory T cells in poly(ADP-Ribose) polymerase-1 deficiency.Foxp3+ 调节性 T 细胞在多聚（ADP-核糖）聚合酶 1 缺陷中的增加。
J Immunol. 2010 Apr 1;184(7):3470-7. doi: 10.4049/jimmunol.0901568. Epub 2010 Mar 5.
10
Aire's partners in the molecular control of immunological tolerance.Aire 在免疫耐受的分子控制中的合作伙伴。
Cell. 2010 Jan 8;140(1):123-35. doi: 10.1016/j.cell.2009.12.030.
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