Khera Smaira, Chang Nan-Shan
Laboratory of Molecular Immunology, Guthrie Research Institute, Sayre, Pennsylvania 18840, USA.
Ann N Y Acad Sci. 2003 May;995:11-21. doi: 10.1111/j.1749-6632.2003.tb03206.x.
TGF-beta induces growth suppression and apoptosis of various types of cells, but supports fibroblast growth. We previously isolated TIAF1 (TGF-beta1-induced antiapoptotic factor 1), which protects murine L929 fibroblasts from TNF cytotoxicity. Here, we show that TIAF1 induced growth inhibition and apoptosis of monocytic U937 and other types of cells. In contrast, like TGF-beta1, TIAF1 supported transforming growth of L929 fibroblasts. TIAF1 increased the expression of p53, Cip1/p21, and Smad proteins; suppressed ERK phosphorylation; and altered TGF-beta1-mediated Smad2/3 phosphorylation in U937 cells. Antisense TIAF1 mRNA significantly enhanced the proliferation of mink lung Mv1Lu epithelial cells. Together, these observations indicate that TIAF1 participates in the TGF-beta-mediated growth regulation.
转化生长因子β(TGF-β)可诱导多种类型细胞的生长抑制和凋亡,但能促进成纤维细胞生长。我们之前分离出了TIAF1(TGF-β1诱导的抗凋亡因子1),它可保护小鼠L929成纤维细胞免受肿瘤坏死因子(TNF)的细胞毒性作用。在此,我们发现TIAF1可诱导单核细胞U937及其他类型细胞的生长抑制和凋亡。相反,与TGF-β1一样,TIAF1可促进L929成纤维细胞的转化生长。TIAF1可增加U937细胞中p53、Cip1/p21和Smad蛋白的表达;抑制细胞外信号调节激酶(ERK)磷酸化;并改变TGF-β1介导的Smad2/3磷酸化。反义TIAF1 mRNA可显著增强水貂肺Mv1Lu上皮细胞的增殖。综上所述,这些观察结果表明TIAF1参与了TGF-β介导的生长调节。