TEAD/TEF transcription factors utilize the activation domain of YAP65, a Src/Yes-associated protein localized in the cytoplasm
TEAD/TEF transcription factors utilize the activation domain of YAP65, a Src/Yes-associated protein localized in the cytoplasm
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DOI：
10.1101/gad.888601
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发表时间：
2001-05-15
影响因子：
10.5
通讯作者：
DePamphilis, ML
中科院分区：
文献类型：
--
作者：
Vassilev, A;Kaneko, KJ;DePamphilis, ML
哺乳动物表达四种高度保守的TEAD/TEF转录因子，它们结合相同的DNA序列，但在发育过程中具有不同的功能。从小鼠细胞中纯化的TEAD - 2/TEF - 4蛋白主要与YAP65（一种强大的转录共激活因子）氨基末端的一个新的TEAD结合结构域相关联。YAP65与所有四种TEAD蛋白的羧基末端特异性相互作用。这种相互作用以及TEAD的序列特异性DNA结合对于小鼠细胞中的转录激活都是必需的。在通常不支持TEAD依赖性转录的淋巴细胞（例如MPC11）中表达YAP导致TEAD活性诱导高达300倍。相反，TEAD过表达抑制了YAP活性。因此，YAP中的羧基末端酸性激活结构域是TEAD转录因子的转录激活结构域。然而，尽管TEAD集中在细胞核中，但过量的YAP65作为与细胞质定位蛋白14 - 3 - 3的复合物积累在细胞质中。由于TEAD依赖性转录受YAP65限制，并且YAP65还结合Src/Yes蛋白酪氨酸激酶，我们提出YAP65响应有丝分裂原信号调节TEAD依赖性转录。
Mammals express four highly conserved TEAD/TEF transcription factors that bind the same DNA sequence, but serve different functions during development. TEAD-2/TEF-4 protein purified from mouse cells was associated predominantly with a novel TEAD-binding domain at the amino terminus of YAP65, a powerful transcriptional coactivator. YAP65 interacted specifically with the carboxyl terminus of all four TEAD proteins. Both this interaction and sequence-specific DNA binding by TEAD were required for transcriptional activation in mouse cells. Expression of YAP in lymphocytic cells that normally do not support TEAD-dependent transcription (e.g., MPC11) resulted in up to 300-fold induction of TEAD activity. Conversely, TEAD overexpression squelched YAP activity. Therefore, the carboxy-terminal acidic activation domain in YAP is the transcriptional activation domain for TEAD transcription factors. However, whereas TEAD was concentrated in the nucleus, excess YAP65 accumulated in the cytoplasm as a complex with the cytoplasmic localization protein, 14-3-3. Because TEAD-dependent transcription was limited by YAP65, and YAP65 also binds Src/Yes protein tyrosine kinases, we propose that YAP65 regulates TEAD-dependent transcription in response to mitogenic signals.