FEBS Open Bio (Jun 2023)

Identification and functional comparison of novel alternatively spliced isoforms of human YAP

  • Lianlian Liu,
  • Junlei Zhang,
  • Jiaqi Wang,
  • Yanping Tian,
  • Jiali Wang,
  • Yixiao Xu,
  • Yuda Cheng,
  • Meng Yu,
  • Jiangjun Wang,
  • Yi Yang,
  • Xueyue Wang,
  • Ran Yang,
  • Wei Wu,
  • Chen Zhang,
  • Yan Hu,
  • Rui Jian,
  • Lan Xiao,
  • Yan Ruan

DOI
https://doi.org/10.1002/2211-5463.13618
Journal volume & issue
Vol. 13, no. 6
pp. 1001 – 1014

Abstract

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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.

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