USP36 facilitates esophageal squamous carcinoma progression via stabilizing YAP
Abstract Esophageal squamous carcinoma (ESCC) is the major subtype of esophageal cancer in China, accounting for 90% of cases. Recent studies revealed that abnormalities in the Hippo/YAP axis are pervasive in ESCC and are recognized as the important driver of ESCC progression. Since the activity of...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-12-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-05474-5 |
| _version_ | 1811178992586194944 |
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| author | Wenhao Zhang Junwen Luo Zhaohua Xiao Yifeng Zang Xin Li Yougjia Zhou Jie Zhou Zhongxian Tian Jian Zhu Xiaogang Zhao |
| author_facet | Wenhao Zhang Junwen Luo Zhaohua Xiao Yifeng Zang Xin Li Yougjia Zhou Jie Zhou Zhongxian Tian Jian Zhu Xiaogang Zhao |
| author_sort | Wenhao Zhang |
| collection | DOAJ |
| description | Abstract Esophageal squamous carcinoma (ESCC) is the major subtype of esophageal cancer in China, accounting for 90% of cases. Recent studies revealed that abnormalities in the Hippo/YAP axis are pervasive in ESCC and are recognized as the important driver of ESCC progression. Since the activity of Hippo signaling is controlled by phosphorylation cascade, it is a mystery why the major effector YAP is still over-activated when the cascade is inhibited. Several studies suggested that in addition to phosphorylation, other protein modifications such as ubiquitination also play important roles in manipulating Hippo/YAP signaling activity. Since YAP protein stability is controlled via an appropriate balance between E3 ubiquitin ligases and deubiquitinases, we performed deubiquitinase siRNA screening and identified USP36 as a deubiquitinase significantly related to Hippo/YAP signaling activity and ESCC progression. USP36 expression was elevated in ESCC samples and correlated with poor differentiation. USP36 expression was correlated with YAP protein levels in ESCC samples. Molecular studies demonstrated that USP36 associated with the YAP protein and enhanced YAP protein stability by blocking the K48-linked polyubiquitination of YAP. In conclusion, our study revealed a novel deubiquitinase in regulating Hippo signaling in ESCC, which could be an encouraging drug target for Hippo-driven ESCC. |
| first_indexed | 2024-04-11T06:27:21Z |
| format | Article |
| id | doaj.art-6c65be7bd98e478b9a74784cce3b44b2 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-11T06:27:21Z |
| publishDate | 2022-12-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-6c65be7bd98e478b9a74784cce3b44b22022-12-22T04:40:18ZengNature Publishing GroupCell Death and Disease2041-48892022-12-01131211410.1038/s41419-022-05474-5USP36 facilitates esophageal squamous carcinoma progression via stabilizing YAPWenhao Zhang0Junwen Luo1Zhaohua Xiao2Yifeng Zang3Xin Li4Yougjia Zhou5Jie Zhou6Zhongxian Tian7Jian Zhu8Xiaogang Zhao9Department of Thoracic Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Thoracic Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Thoracic Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of General Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong UniversityXinxiang Key Laboratory of Tumor Migration and Invasion Precision Medicine, School of Laboratory Medicine, Xinxiang Medical UniversityDepartment of Thoracic Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Thoracic Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Thoracic Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of General Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Thoracic Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong UniversityAbstract Esophageal squamous carcinoma (ESCC) is the major subtype of esophageal cancer in China, accounting for 90% of cases. Recent studies revealed that abnormalities in the Hippo/YAP axis are pervasive in ESCC and are recognized as the important driver of ESCC progression. Since the activity of Hippo signaling is controlled by phosphorylation cascade, it is a mystery why the major effector YAP is still over-activated when the cascade is inhibited. Several studies suggested that in addition to phosphorylation, other protein modifications such as ubiquitination also play important roles in manipulating Hippo/YAP signaling activity. Since YAP protein stability is controlled via an appropriate balance between E3 ubiquitin ligases and deubiquitinases, we performed deubiquitinase siRNA screening and identified USP36 as a deubiquitinase significantly related to Hippo/YAP signaling activity and ESCC progression. USP36 expression was elevated in ESCC samples and correlated with poor differentiation. USP36 expression was correlated with YAP protein levels in ESCC samples. Molecular studies demonstrated that USP36 associated with the YAP protein and enhanced YAP protein stability by blocking the K48-linked polyubiquitination of YAP. In conclusion, our study revealed a novel deubiquitinase in regulating Hippo signaling in ESCC, which could be an encouraging drug target for Hippo-driven ESCC.https://doi.org/10.1038/s41419-022-05474-5 |
| spellingShingle | Wenhao Zhang Junwen Luo Zhaohua Xiao Yifeng Zang Xin Li Yougjia Zhou Jie Zhou Zhongxian Tian Jian Zhu Xiaogang Zhao USP36 facilitates esophageal squamous carcinoma progression via stabilizing YAP Cell Death and Disease |
| title | USP36 facilitates esophageal squamous carcinoma progression via stabilizing YAP |
| title_full | USP36 facilitates esophageal squamous carcinoma progression via stabilizing YAP |
| title_fullStr | USP36 facilitates esophageal squamous carcinoma progression via stabilizing YAP |
| title_full_unstemmed | USP36 facilitates esophageal squamous carcinoma progression via stabilizing YAP |
| title_short | USP36 facilitates esophageal squamous carcinoma progression via stabilizing YAP |
| title_sort | usp36 facilitates esophageal squamous carcinoma progression via stabilizing yap |
| url | https://doi.org/10.1038/s41419-022-05474-5 |
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