Guanine Nucleotide Exchange Factor, Tiam1, Directly Binds to c-Myc and Interferes with c-Myc-mediated Apoptosis in Rat-1 Fibroblasts*
Guanine Nucleotide Exchange Factor, Tiam1, Directly Binds to c-Myc and Interferes with c-Myc-mediated Apoptosis in Rat-1 Fibroblasts*
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DOI：
10.1074/jbc.m206733200
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发表时间：
2003-02
期刊：
影响因子：
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通讯作者：
Y. Otsuki;Masamitsu Tanaka;T. Kamo;C. Kitanaka;Y. Kuchino;H. Sugimura
中科院分区：
文献类型：
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作者：
Y. Otsuki;Masamitsu Tanaka;T. Kamo;C. Kitanaka;Y. Kuchino;H. Sugimura
转录因子 c-Myc 对于细胞生长、细胞周期进程、肿瘤形成和细胞凋亡的控制很重要。最近，c-Myc 结合蛋白（与 c-Myc 的 N 端结构域或 C 端结构域结合）被认为是实现这些多种 c-Myc 功能机制的关键分子。我们在本研究中报告了另一种蛋白质 Tiam1，它是 Rac1 的一种特定鸟嘌呤核苷酸交换因子，可与 c-Myc 结合并调节其多种生物学功能。我们能够检测到 c-Myc 和 Tiam1 之间的直接结合和体内关联。细胞提取物揭示了 c-Myc 的 Myc box II 相互作用中的必要作用。 Tiam1 在 Rat1 细胞和小鼠大脑神经元细胞中的核内定位的额外发现表明这种相互作用可能发生在细胞核中。 Tiam1 的过表达抑制了 c-Myc 的荧光素酶活性，并通过这种蛋白质-蛋白质相互作用抑制了 c-Myc 凋亡活性。综上所述，我们得出结论，Tiam1 是另一个 c-Myc 调节因子，在细胞核中发挥作用，控制 c-Myc 相关的细胞凋亡。
The transcription factor c-Myc is important for the control of cell growth, cell cycle progression, neoplasia, and apoptotic cell death. Recently, c-Myc-binding proteins, which bind either to the N-terminal domain or the C-terminal domain of c-Myc, have been proposed as the key molecules to realize the mechanisms of these multiple c-Myc functions. We report in the present study on another protein, Tiam1, which is a specific guanine nucleotide exchange factor of Rac1 and which binds to c-Myc and modulates several of its biological functions. We were able to detect the direct binding and in vivo association between c-Myc and Tiam1. The necessary role in this interaction of the Myc box II of c-Myc was revealed in the cell extracts. The additional discovery of the intranuclear localization of Tiam1 in Rat1 cells and in neuronal cells of the mouse brain suggests this interaction may occur in the nucleus. Overexpression of Tiam1 repressed the luciferase activity of c-Myc and also inhibited the c-Myc apoptotic activity through this protein-protein interaction. Taken together, we concluded that Tiam1 is another c-Myc regulator, working in the nuclei to control c-Myc-related apoptosis.