New Branch to TGF-β Pathway

IF 6.7 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Science Signaling Pub Date : 2006-06-06 DOI:10.1126/stke.3382006tw191
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引用次数: 0

Abstract

Cytokines of the transforming growth factor-β (TGF-β) family have important roles in development, cancer, and other cellular processes. Abundant evidence shows that stimulated TGF-β receptors phosphorylate Smad2 and Smad3 proteins, which act in complexes with Smad4 to regulate transcription in the nucleus. New results from He et al. point to a distinct mechanism by which TGF-β can control gene regulation. The authors searched for binding partners for Smads 2 and 3 and identified the protein transcriptional intermediary factor 1γ (TIF1γ, also called TRIM33, RFG7, PTC7, or ectodermin), a protein that functions as a cofactor with nuclear receptors and other transcription factors and as a component of the histone deacetylase N-CoR1/HDAC3 complex. Exposure of human hematopoietic progenitor cells to TGF increased the usual association of Smads 2 and 3 with Smad4 but also increased formation of complexes of Smad2/3 with TIF1γ in an apparently competitive manner. In human hematopoietic stem cells, TGF-β promotes differentiation, and this effect required TIF1γ. Reduced abundance of TIF1γ after infection of cells with retroviruses encoding shRNA inhibited differentiation of the cells in culture. Depletion of Smad4 had no effect on differentiation. In other culture conditions in which stem cell proliferation is enhanced, TGF-β inhibits proliferation. This effect required the presence of Smads 2 and 3 but was not affected by depletion of TIF1γ. The authors therefore conclude that activated Smads 2 and 3 can trigger two separate transcriptional responses with distinct biological outcomes, depending on whether they act in association with Smad4 or TIF1γ.
W. He, D. C. Dorn, H. Erdjument-Bromage, P. Tempst, M. A. S. Moore, J. Massagué, Hematopoiesis controlled by distinct TIF1γ and Smad4 branches of the TGFβ pathway. Cell 125, 929-941 (2006). [PubMed]
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TGF-β 通路的新分支
转化生长因子-β(TGF-β)家族的细胞因子在发育、癌症和其他细胞过程中发挥着重要作用。大量证据表明,受刺激的 TGF-β 受体会使 Smad2 和 Smad3 蛋白磷酸化,而 Smad2 和 Smad3 蛋白与 Smad4 复合物一起调节细胞核中的转录。He 等人的新研究成果指出了 TGF-β 控制基因调控的独特机制。作者寻找了Smads 2和3的结合伙伴,发现了蛋白质转录中间因子1γ(TIF1γ,又称TRIM33、RFG7、PTC7或ectodermin),这种蛋白质是核受体和其他转录因子的辅助因子,也是组蛋白去乙酰化酶N-CoR1/HDAC3复合物的组成部分。将人类造血祖细胞暴露于 TGF 会增加 Smads 2 和 3 与 Smad4 的通常结合,但也会以明显的竞争方式增加 Smad2/3 与 TIF1γ 复合物的形成。在人类造血干细胞中,TGF-β能促进分化,而这种作用需要TIF1γ。用编码 shRNA 的逆转录病毒感染细胞后,TIF1γ 的丰度降低,抑制了培养细胞的分化。消耗Smad4对分化没有影响。在干细胞增殖增强的其他培养条件下,TGF-β抑制增殖。这种效应需要Smads 2和3的存在,但TIF1γ的耗竭对其没有影响。因此,作者得出结论,活化的 Smads 2 和 3 可以触发两种不同的转录反应,并产生不同的生物学结果,这取决于它们是与 Smad4 还是 TIF1γ 共同作用。W. He、D. C. Dorn、H. Erdjument-Bromage、P. Tempst、M. A. S. Moore、J. Massagué,TGFβ通路中不同的 TIF1γ 和 Smad4 分支控制的造血。细胞 125,929-941(2006 年)。[PubMed].
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来源期刊
Science Signaling
Science Signaling BIOCHEMISTRY & MOLECULAR BIOLOGY-CELL BIOLOGY
CiteScore
9.50
自引率
0.00%
发文量
148
审稿时长
3-8 weeks
期刊介绍: "Science Signaling" is a reputable, peer-reviewed journal dedicated to the exploration of cell communication mechanisms, offering a comprehensive view of the intricate processes that govern cellular regulation. This journal, published weekly online by the American Association for the Advancement of Science (AAAS), is a go-to resource for the latest research in cell signaling and its various facets. The journal's scope encompasses a broad range of topics, including the study of signaling networks, synthetic biology, systems biology, and the application of these findings in drug discovery. It also delves into the computational and modeling aspects of regulatory pathways, providing insights into how cells communicate and respond to their environment. In addition to publishing full-length articles that report on groundbreaking research, "Science Signaling" also features reviews that synthesize current knowledge in the field, focus articles that highlight specific areas of interest, and editor-written highlights that draw attention to particularly significant studies. This mix of content ensures that the journal serves as a valuable resource for both researchers and professionals looking to stay abreast of the latest advancements in cell communication science.
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