Laboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology, Army Medical University, Chongqing, China.
Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Army Medical University, Chongqing, China.
FEBS Open Bio. 2023 Jun;13(6):1001-1014. doi: 10.1002/2211-5463.13618. Epub 2023 May 8.
As a key effector of the Hippo pathway, yes-associated protein (YAP) is a major regulator of cell proliferation and apoptosis. In this study, 23 hYAP isoforms were identified in HEK293 cells, with 14 isoforms being reported for the first time. These isoforms were classified into hYAP-a and hYAP-b isoforms based on the variation in exon 1. The two groups of isoforms showed distinctly different subcellular localizations. hYAP-a isoforms could activate TEAD- or P73-mediated transcription, affect the proliferation rate, and enhance the cellular chemosensitivity of HEK293 cells. Moreover, different activation abilities and pro-cytotoxic effects were observed among hYAP-a isoforms. However, hYAP-b isoforms were not found to exert any significant biological effects. Our findings add to the knowledge of YAP gene structure and protein-coding capacity and will help in the elucidation of the function and related molecular mechanisms of the Hippo-YAP signaling pathway.
作为 Hippo 通路的关键效应因子，Yes 相关蛋白（YAP）是细胞增殖和凋亡的主要调节因子。本研究在 HEK293 细胞中鉴定出 23 种 hYAP 异构体，其中 14 种是首次报道。这些异构体根据外显子 1 的变化分为 hYAP-a 和 hYAP-b 异构体。两组异构体表现出明显不同的亚细胞定位。hYAP-a 异构体可以激活 TEAD 或 P73 介导的转录，影响增殖率，并增强 HEK293 细胞的化学敏感性。此外，hYAP-a 异构体之间观察到不同的激活能力和促细胞毒性作用。然而，hYAP-b 异构体未表现出任何显著的生物学效应。我们的研究结果增加了对 YAP 基因结构和蛋白编码能力的了解，有助于阐明 Hippo-YAP 信号通路的功能和相关分子机制。
