Institute of Molecular and Cell Biology, Singapore.
Sci Signal. 2013 Sep 3;6(291):pe27. doi: 10.1126/scisignal.2004573.
The Hippo pathway regulates cell proliferation and apoptosis during development, tissue regeneration, and carcinogenesis. Nuclear translocation of the transcription factors Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) and their subsequent interaction with TEA domain (TEAD) transcriptional factors program pro-proliferative and antiapoptotic transcription. Scaffold proteins angiomotin (Amot) and angiomotin-related AmotL1 and AmotL2 were recently identified as negative regulators of YAP and TAZ by preventing their nuclear translocation. In this issue of Science Signaling, Yi et al. show that Amot may also promote nuclear translocation of YAP and act as a transcriptional cofactor of the YAP-TEAD complex to facilitate proliferation of biliary epithelial cells and cancer development of the liver either in response to tissue injury or in the absence of the tumor suppressor Merlin. These seemingly controversial results highlight that our understanding of Amot proteins in the Hippo pathway is so far limited.
Hippo 通路在发育、组织再生和致癌作用过程中调节细胞增殖和凋亡。转录因子 Yes 相关蛋白 (YAP) 和转录共激活因子 PDZ 结合基序 (TAZ) 的核易位及其随后与 TEA 结构域 (TEAD) 转录因子的相互作用，规划促增殖和抗凋亡的转录。支架蛋白 angiomotin (Amot) 和 angiomotin 相关的 AmotL1 和 AmotL2 最近被确定为 YAP 和 TAZ 的负调控因子，通过阻止它们的核易位。在本期《科学信号》中，Yi 等人表明，Amot 也可能促进 YAP 的核易位，并作为 YAP-TEAD 复合物的转录共因子，促进胆管上皮细胞的增殖和肝脏癌症的发展，无论是在组织损伤时还是在肿瘤抑制因子 Merlin 缺失时。这些看似矛盾的结果强调，我们对 Hippo 通路中 Amot 蛋白的理解目前还很有限。
