PUBLICATION
NEDD8 enhances Hippo signaling by mediating YAP1 neddylation
- Authors
- Chen, M., Liu, Y., Zuo, M., Guo, C., Du, Y., Xu, H., Liu, B., Li, M., Xiao, W., Yu, G.
- ID
- ZDB-PUB-240704-7
- Date
- 2024
- Source
- The Journal of biological chemistry 300(8): 107512 (Journal)
- Registered Authors
- Xiao, Wuhan, Yu, Guangqing
- Keywords
- Hippo signaling, NEDD8, YAP1, neddylation
- MeSH Terms
-
- Apoptosis
- Protein Serine-Threonine Kinases*/genetics
- Protein Serine-Threonine Kinases*/metabolism
- Humans
- YAP-Signaling Proteins*/metabolism
- HEK293 Cells
- Female
- Zebrafish*/metabolism
- Signal Transduction*
- Hippo Signaling Pathway
- Phosphoproteins/genetics
- Phosphoproteins/metabolism
- Cyclopentanes*/metabolism
- NEDD8 Protein*/genetics
- NEDD8 Protein*/metabolism
- Adaptor Proteins, Signal Transducing*/genetics
- Adaptor Proteins, Signal Transducing*/metabolism
- Animals
- Pyrimidines/pharmacology
- Protein Processing, Post-Translational
- Transcription Factors*/genetics
- Transcription Factors*/metabolism
- PubMed
- 38960037 Full text @ J. Biol. Chem.
Citation
Chen, M., Liu, Y., Zuo, M., Guo, C., Du, Y., Xu, H., Liu, B., Li, M., Xiao, W., Yu, G. (2024) NEDD8 enhances Hippo signaling by mediating YAP1 neddylation. The Journal of biological chemistry. 300(8):107512.
Abstract
The Hippo-YAP signaling pathway plays a central role in many biological processes such as regulating cell fate, organ size and tissue growth, and its key components are spatiotemporally expressed and post-translationally modified during these processes. Neddylation is a post-translational modification that involves the covalent attachment of NEDD8 to target proteins by NEDD8-specific E1-E2-E3 enzymes. Whether neddylation is involved in Hippo-YAP signaling remains poorly understood. Here, we provide evidence supporting the critical role of NEDD8 in facilitating the Hippo-YAP signaling pathway by mediating neddylation of the transcriptional coactivator Yes-associated protein 1 (YAP1). Overexpression of NEDD8 induces YAP1 neddylation and enhances YAP1 transactivity, but inhibition of neddylation suppresses YAP1 transactivity and attenuates YAP1 nuclear accumulation. Furthermore, inhibition of YAP1 signaling promotes MLN4924-induced GCs apoptosis and disruption of nedd8 in zebrafish results in downregulation of yap1-activated genes and upregulation of yap1-repressed genes. Further assays show that the xiap ligase promotes nedd8 conjugates to yap1 and that yap1 neddylation. In addition, we identify lysine 159 as a major neddylation site on YAP1. These findings reveal a novel mechanism for neddylation in the regulation of Hippo-YAP signaling.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping