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YAP/TAZ:分子途径与疾病治疗

YAP/TAZ: Molecular pathway and disease therapy.

作者信息

Wei Yuzi, Hui Victoria Lee Zhi, Chen Yilin, Han Ruiying, Han Xianglong, Guo Yongwen

机构信息

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology Sichuan University Chengdu Sichuan China.

Department of Orthodontics West China Hospital of Stomatology Sichuan University Chengdu Sichuan China.

出版信息

MedComm (2020). 2023 Aug 9;4(4):e340. doi: 10.1002/mco2.340. eCollection 2023 Aug.

Abstract

The Yes-associated protein and its transcriptional coactivator with PDZ-binding motif (YAP/TAZ) are two homologous transcriptional coactivators that lie at the center of a key regulatory network of Hippo, Wnt, GPCR, estrogen, mechanical, and metabolism signaling. YAP/TAZ influences the expressions of downstream genes and proteins as well as enzyme activity in metabolic cycles, cell proliferation, inflammatory factor expression, and the transdifferentiation of fibroblasts into myofibroblasts. YAP/TAZ can also be regulated through epigenetic regulation and posttranslational modifications. Consequently, the regulatory function of these mechanisms implicates YAP/TAZ in the pathogenesis of metabolism-related diseases, atherosclerosis, fibrosis, and the delicate equilibrium between cancer progression and organ regeneration. As such, there arises a pressing need for thorough investigation of YAP/TAZ in clinical settings. In this paper, we aim to elucidate the signaling pathways that regulate YAP/TAZ and explore the mechanisms of YAP/TAZ-induce diseases and their potential therapeutic interventions. Furthermore, we summarize the current clinical studies investigating treatments targeting YAP/TAZ. We also address the limitations of existing research on YAP/TAZ and propose future directions for research. In conclusion, this review aims to provide fresh insights into the signaling mediated by YAP/TAZ and identify potential therapeutic targets to present innovative solutions to overcome the challenges associated with YAP/TAZ.

摘要

Yes相关蛋白及其含PDZ结合基序的转录共激活因子(YAP/TAZ)是两种同源转录共激活因子,处于Hippo、Wnt、GPCR、雌激素、机械和代谢信号关键调控网络的核心位置。YAP/TAZ影响下游基因和蛋白质的表达以及代谢循环中的酶活性、细胞增殖、炎症因子表达和成纤维细胞向肌成纤维细胞的转分化。YAP/TAZ也可通过表观遗传调控和翻译后修饰进行调节。因此,这些机制的调节功能使YAP/TAZ参与了代谢相关疾病、动脉粥样硬化、纤维化以及癌症进展与器官再生之间微妙平衡的发病过程。正因如此,迫切需要在临床环境中对YAP/TAZ进行深入研究。在本文中,我们旨在阐明调节YAP/TAZ的信号通路,探索YAP/TAZ诱导疾病的机制及其潜在的治疗干预措施。此外,我们总结了目前针对YAP/TAZ治疗的临床研究。我们还讨论了现有YAP/TAZ研究的局限性,并提出了未来的研究方向。总之,本综述旨在为YAP/TAZ介导的信号传导提供新的见解,并确定潜在的治疗靶点,以提出创新解决方案来克服与YAP/TAZ相关的挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9857/10412783/6b59f7692fd8/MCO2-4-e340-g007.jpg

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