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Yes 相关蛋白和含 PDZ 结合模体的转录共激活因子——心血管疾病的新靶点

Yes-associated protein and transcriptional coactivator with PDZ-binding motif as new targets in cardiovascular diseases.

机构信息

Institute of Basic and Translational Medicine, Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Shaanxi Key Laboratory of Brain Disorders, Xi'an Medical University, Xi'an, Shaanxi 710021, China.

School of Basic and Medical Sciences, Xi'an Medical University, Xi'an, Shaanxi 710021, China.

出版信息

Pharmacol Res. 2020 Sep;159:105009. doi: 10.1016/j.phrs.2020.105009. Epub 2020 Jun 15.

Abstract

As transcriptional co-activators, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) can regulate cell proliferation, migration, differentiation, and apoptosis by interacting with the transcription factors [e.g., transcriptional enhancer associate domain (TEAD) family members]. Polarity and junctional proteins, mechanical stress, and G protein-coupled receptors (GPCRs) are Hippo pathway-dependent upstream regulatory pathways of YAP and TAZ activity. In addition, posttranslational modifications (such as phosphorylation, O-GlcNAcylation, acetylation, methylation, geranylgeranylation, and palmitoylation) also participate in the regulation of YAP and TAZ activity. YAP and TAZ have recently been implicated in the pathological process of vascular and heart diseases. The activation of YAP and TAZ promotes atherosclerosis, angiogenesis, restenosis, pulmonary hypertension, myocardial hypertrophy, and myocardial fibrosis, whereas the inhibition of YAP and TAZ is involved in aortic aneurysms, aortic dissection, myocardial ischemia-reperfusion injury, and myocardial infarction. Thus, both YAP and TAZ may be potential targets for treating cardiovascular diseases. In this review, we discuss the latest findings regarding YAP and TAZ and the potential drugs that target these compounds to treat cardiovascular diseases. This review lays the foundation for a future direction of cardiovascular disease research.

摘要

作为转录共激活因子,Yes 相关蛋白 (YAP) 和含 PDZ 结合基序的转录共激活因子 (TAZ) 可以通过与转录因子 [如转录增强子相关域 (TEAD) 家族成员] 相互作用来调节细胞增殖、迁移、分化和凋亡。极性和连接蛋白、机械应激和 G 蛋白偶联受体 (GPCR) 是 Hippo 通路依赖性 YAP 和 TAZ 活性的上游调节途径。此外,翻译后修饰(如磷酸化、O-GlcNAc 化、乙酰化、甲基化、香叶基香叶基化和棕榈酰化)也参与 YAP 和 TAZ 活性的调节。YAP 和 TAZ 最近被牵连到血管和心脏疾病的病理过程中。YAP 和 TAZ 的激活促进动脉粥样硬化、血管生成、再狭窄、肺动脉高压、心肌肥大和心肌纤维化,而 YAP 和 TAZ 的抑制参与了主动脉瘤、主动脉夹层、心肌缺血再灌注损伤和心肌梗死。因此,YAP 和 TAZ 都可能是治疗心血管疾病的潜在靶点。在这篇综述中,我们讨论了关于 YAP 和 TAZ 的最新发现,以及针对这些化合物治疗心血管疾病的潜在药物。这篇综述为心血管疾病研究的未来方向奠定了基础。

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