TGF-β-induced apoptosis is mediated by the adapter protein Daxx that facilitates JNK activation
TGF-β-induced apoptosis is mediated by the adapter protein Daxx that facilitates JNK activation
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DOI：
10.1038/35087019
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发表时间：
2001-08-01
影响因子：
21.3
通讯作者：
Weinberg, RA
中科院分区：
文献类型：
--
作者：
Perlman, R;Schiemann, WP;Weinberg, RA
转化生长因子-β（TGF-β）是一种多功能生长因子，其通过其对许多不同上皮细胞类型的细胞生长抑制作用和其在多种其他细胞类型中诱导程序性细胞死亡的能力在生长控制中起主要作用。在这里，我们已经使用了一个屏幕的蛋白质，与II型TGF-β受体的细胞质结构域的物理相互作用，以分离的基因编码Daxx -一种蛋白质与Fas受体介导的激活Jun氨基末端激酶（JNK）和程序性细胞死亡诱导的Fas。Daxx的羧基末端部分在B细胞淋巴瘤中作为TGF-β诱导的细胞凋亡的显性负性抑制剂，并且Daxx的反义寡核苷酸抑制小鼠肝细胞中TGF-β诱导的细胞凋亡。此外，Daxx参与介导TGF-β激活JNK。我们的研究结果将Daxx与TGF-β促凋亡信号通路直接关联，并在TGF-β受体和凋亡机制之间建立了生物化学联系。
Transforming growth factor-beta (TGF-beta) is a multifunctional growth factor that has a principal role in growth control through both its cytostatic effect on many different epithelial cell types and its ability to induce programmed cell death in a variety of other cell types. Here we have used a screen for proteins that interact physically with the cytoplasmic domain of the type II TGF-beta receptor to isolate the gene encoding Daxx - a protein associated with the Fas receptor that mediates activation of Jun amino-terminal kinase (JNK) and programmed cell death induced by Fas. The carboxy-terminal portion of Daxx functions as a dominant-negative inhibitor of TGF-beta -induced apoptosis in B-cell lymphomas, and antisense oligonucleotides to Daxx inhibit TGF-beta -induced apoptosis in mouse hepatocytes. Furthermore, Daxx is involved in mediating JNK activation by TGF-beta. Our findings associate Daxx directly with the TGF-beta apoptotic-signalling pathway, and make a biochemical connection between the receptors for TGF-beta and the apoptotic machinery.