TAZ: a novel transcriptional co-activator regulated by interactions with 14-3-3 and PDZ domain proteins
TAZ: a novel transcriptional co-activator regulated by interactions with 14-3-3 and PDZ domain proteins
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DOI：
10.1093/emboj/19.24.6778
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发表时间：
2000-12-15
期刊：
影响因子：
11.4
通讯作者：
Yaffe, MB
中科院分区：
文献类型：
--
作者：
Kanai, F;Marignani, PA;Yaffe, MB
14-3-3蛋白高度保守且广泛表达，通过结合参与信号转导的细胞内磷蛋白来调节分化、细胞周期进程和凋亡。通过筛选体外翻译的cDNA库结合14-3-3的能力，我们确定了一种新的转录辅激活因子，TAZ（转录辅激活因子与PDZ结合基序）作为14-3-3-结合分子。TAZ与Yes相关蛋白（雅普）具有同源性，含有WW结构域，通过与转录因子上存在的PPXY基序结合而作为转录共激活因子发挥功能。14-3-3结合需要TAZ在单个丝氨酸残基上磷酸化，导致通过14-3-3介导的核输出抑制TAZ转录共激活。TAZ的C-末端含有高度保守的PDZ结合基序，其将TAZ定位到离散的核灶中，并且对于TAZ刺激的基因转录是必需的。TAZ使用相同的基序结合含PDZ结构域的蛋白NHERF-2，NHERF-2是一种将质膜离子通道和受体束缚在细胞骨架肌动蛋白上的分子。TAZ可能以可由14-3-3调节的方式将质膜和细胞骨架处的事件与核转录联系起来。
The highly conserved and ubiquitously expressed 14-3-3 proteins regulate differentiation, cell cycle progression and apoptosis by binding intracellular phosphoproteins involved in signal transduction. By screening in vitro translated cDNA pools for the ability to bind 14-3-3, we identified a novel transcriptional co-activator, TAZ (transcriptional co-activator with PDZ-binding motif) as a 14-3-3-binding molecule. TAZ shares homology with Yes-associated protein (YAP), contains a WW domain and functions as a transcriptional co-activator by binding to the PPXY motif present on transcription factors. 14-3-3 binding requires TAZ phosphorylation on a single serine residue, resulting in the inhibition of TAZ transcriptional co-activation through 14-3-3-mediated nuclear export. The C-terminus of TAZ contains a highly conserved PDZ-binding motif that localizes TAZ into discrete nuclear foci and is essential for TAZ-stimulated gene transcription. TAZ uses this same motif to bind the PDZ domain-containing protein NHERF-2, a molecule that tethers plasma membrane ion channels and receptors to cytoskeletal actin. TAZ may link events at the plasma membrane and cytoskeleton to nuclear transcription in a manner that can be regulated by 14-3-3.