NEDD4 promotes reactive astrogliosis by enhancing K63-linked ubiquitination and inhibiting chaperone-mediated autophagy degradation of YAP1

International Journal of Biological Sciences 2026 Open access

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Authors: Wu Ye, Yigang Li, Wei Wang, Dishui Pan, Xiaokun Wang, Yao Gu, Yufeng Zhu, Haofan Wang, Xin Lu, Dongdong Jiang, Pengyu Tang, Haoming Shu
+2 more Jun Ma, Weihua Cai
DOI: 10.7150/ijbs.123639
Cited by: 3

Abstract

deficiency. Mechanistically, NEDD4 interacts with YAP1 and mediates K63-linked ubiquitination at lysine 254, thereby preventing its degradation via the chaperone-mediated autophagy (CMA) pathway involving HSC70. Furthermore, we demonstrate that the ROS-FOXM1 signaling cascade drives NEDD4 expression, thereby stabilizing YAP1 and promoting astrocyte proliferation. In summary, our findings underscore the pivotal role of the ROS-FOXM1-NEDD4-YAP1 signaling cascade in controlling astrocytic activation and tissue regeneration post-SCI, positioning NEDD4 as a viable target to regulate astrogliosis and facilitate neurological restoration after SCI.

Fields of Study & Subjects

Hippo pathway signaling and YAP/TAZ Mesenchymal stem cell research Autophagy in Disease and Therapy

Publication details

Journal / source
International Journal of Biological Sciences
Publisher
Ivyspring International Publisher
Volume
22
Issue
2
Pages
858–875
Publication date
1 January 2026
Language
EN