Yes-associated protein homolog, YAP-1, is involved in the thermotolerance and aging in the nematode Caenorhabditis elegans
Yes-associated protein homolog, YAP-1, is involved in the thermotolerance and aging in the nematode Caenorhabditis elegans
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DOI：
10.1016/j.yexcr.2013.01.020
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发表时间：
2013-04-15
影响因子：
3.7
通讯作者：
Hata, Yutaka
中科院分区：
文献类型：
--
作者：
Iwasa, Hiroaki;Maimaiti, Sainawaer;Hata, Yutaka
哺乳动物Hippo途径包括哺乳动物Ste 20样激酶（MST 1/2）和大肿瘤抑制激酶（LATS 1/2）。LATS 1/2被MST 1/2激活，磷酸化转录辅激活因子-yes相关蛋白（雅普），并诱导雅普被14-3-3募集到细胞质中，从而关闭TEAD依赖的基因转录。虽然Hippo通路的核心组分在后生动物中很保守，但已经讨论了秀丽隐杆线虫缺乏雅普直系同源物，我们发现F13 E6.4基因编码的蛋白在N-末端TEAD结合结构域和WW结构域中显示出与雅普的序列相似性。我们将该基因命名为雅普-1。YAP-1广泛表达于上皮细胞、肌肉、下皮细胞、性腺鞘细胞、受精囊和下皮细胞等各种细胞中。雅普-1分布于细胞质和细胞核。wts-1（LATS直系同源物）和ftt-2（14-3-3直系同源物）敲低导致雅普-1的核积累，支持雅普-1的亚细胞定位以与雅普类似的方式调节。热激也引起雅普-1在细胞核中的积累，但热激后，雅普-1易位到细胞质中。在此恢复过程中，HSP 90同源物HSP 21和HSF-1的敲除阻断了雅普-1的核输出。雅普-1过表达有利于热耐受性，而wts-1和ftt-2敲除诱导的雅普-1过度活跃对热反应有害，而雅普-1缺乏会促进健康衰老。总之，雅普-1与哺乳动物雅普具有部分共同的基本特征，并在热应激反应和健康衰老中发挥作用。(C)2013 Elsevier Inc. All rights reserved.
The mammalian Hippo pathway comprises mammalian Ste20-like kinases (MST1/2) and large tumor suppressor kinases (LATS1/2). LATS1/2, which are activated by MST1/2, phosphorylate a transcriptional co-activator, yes-associated protein (YAP), and induce the recruitment of YAP by 14-3-3 to cytoplasm, so that the TEAD-dependent gene transcriptions are turned off. Although the core components of the Hippo pathway are well conserved in metazoans, it has been discussed that Caenorhabditis elegans lacks YAP ortholog, we found that F13E6.4 gene encodes a protein that shows sequence similarities to YAP in the N-terminal TEAD-binding domain and in the WW domain. We designated this gene as yap-1. YAP-I is widely expressed in various cells such as epithelial cells, muscles, hypodermal cells, gonadal sheath cells, spermatheca, and hypodermal cells. YAP-1 is distributed in cytoplasm and nuclei. wts-1 (LATS ortholog) and ftt-2 (14-3-3 ortholog) knockdowns cause nuclear accumulation of YAP-1, supporting that the subcellular localization of YAP-1 is regulated in a similar way as that of YAP. Heat shock also causes the nuclear accumulation of YAP-1 but after heat shock, YAP-1 translocates to cytoplasm. Knockdowns of DAF-21 (HSP90 ortholog) and HSF-1block the nuclear export of YAP-1 during this recovery. YAP-1 overexpression is beneficial for thermotolerance, whereas YAP-1 hyperactivity induced by wts-1 and ftt-2 knockdowns is deleterious on thermal response and yap-1 deficiency promotes health aging. In short, YAP-1 partially shares basal characters with mammalian YAP and plays a role in thermal stress response and healthy aging. (C) 2013 Elsevier Inc. All rights reserved.