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

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 is...

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Main Authors: 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
Format: Article
Language:English
Published: Wiley 2023-06-01
Series:FEBS Open Bio
Subjects:
Online Access:https://doi.org/10.1002/2211-5463.13618
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author 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
author_facet 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
author_sort Lianlian Liu
collection DOAJ
description 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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spelling doaj.art-ea4aca82387e4a34b1874e5803cd1bc32023-06-05T08:21:04ZengWileyFEBS Open Bio2211-54632023-06-011361001101410.1002/2211-5463.13618Identification and functional comparison of novel alternatively spliced isoforms of human YAPLianlian Liu0Junlei Zhang1Jiaqi Wang2Yanping Tian3Jiali Wang4Yixiao Xu5Yuda Cheng6Meng Yu7Jiangjun Wang8Yi Yang9Xueyue Wang10Ran Yang11Wei Wu12Chen Zhang13Yan Hu14Rui Jian15Lan Xiao16Yan Ruan17Laboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology Army Medical University Chongqing ChinaLaboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology Army Medical University Chongqing ChinaLaboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology Army Medical University Chongqing ChinaLaboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology Army Medical University Chongqing ChinaLaboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology Army Medical University Chongqing ChinaLaboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology Army Medical University Chongqing ChinaLaboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology Army Medical University Chongqing ChinaLaboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology Army Medical University Chongqing ChinaLaboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology Army Medical University Chongqing ChinaExperimental Center of Basic Medicine, College of Basic Medical Sciences Army Medical University Chongqing ChinaDepartment of Pediatrics The General Hospital of PLA Tibet Military Area Command Lhasa ChinaLaboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology Army Medical University Chongqing ChinaThoracic Surgery Department Southwest Hospital, The First Hospital Affiliated to Army Medical University Chongqing ChinaLaboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology Army Medical University Chongqing ChinaDepartment of Military Basic Training and Army Management, Army Health Service Training Base Army Medical University Chongqing ChinaLaboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology Army Medical University Chongqing ChinaDepartment of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Brain and Intelligence Research Key Laboratory of Chongqing Education Commission Army Medical University Chongqing ChinaLaboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology Army Medical University Chongqing ChinaAs 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.https://doi.org/10.1002/2211-5463.13618alternative splicingcell chemosensitivitytranscriptional activation abilityYAP
spellingShingle 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
Identification and functional comparison of novel alternatively spliced isoforms of human YAP
FEBS Open Bio
alternative splicing
cell chemosensitivity
transcriptional activation ability
YAP
title Identification and functional comparison of novel alternatively spliced isoforms of human YAP
title_full Identification and functional comparison of novel alternatively spliced isoforms of human YAP
title_fullStr Identification and functional comparison of novel alternatively spliced isoforms of human YAP
title_full_unstemmed Identification and functional comparison of novel alternatively spliced isoforms of human YAP
title_short Identification and functional comparison of novel alternatively spliced isoforms of human YAP
title_sort identification and functional comparison of novel alternatively spliced isoforms of human yap
topic alternative splicing
cell chemosensitivity
transcriptional activation ability
YAP
url https://doi.org/10.1002/2211-5463.13618
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