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Updated: Jun 24, 2026

Isolation and Culture of Cells from the Nephrogenic Zone of the Embryonic Mouse Kidney
Published on: April 22, 2011
UFMylation orchestrates kidney development through YAP stabilization
Yi Chen1, Longyi Wan1, Wei Chen1
1Zhejiang Key Laboratory of Medical Epigenetics, Department of Cell Biology and Genetics, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, Zhejiang, China.
UFMylation is essential for kidney development by stabilizing the YAP protein, preventing its degradation. This process is crucial for normal kidney organogenesis and transcriptional activation.
Area of Science:
- Biochemistry
- Developmental Biology
- Molecular Biology
Background:
- UFMylation, a post-translational modification, regulates cellular processes.
- UFMylation ligase UFL1 deficiency causes kidney atrophy.
- The role of UFMylation in organogenesis and its substrates are largely unknown.
Purpose of the Study:
- Investigate the role of UFMylation in mammalian kidney development.
- Identify critical UFMylation substrates involved in kidney organogenesis.
- Elucidate the mechanism of UFMylation in regulating key developmental pathways.
Main Methods:
- Genetic ablation of Ufl1 in murine kidneys.
- Identification of YAP as a UFMylation substrate.
- Analysis of YAP stabilization and nuclear accumulation.
- Investigating the role of UFSP1 and UFSP2 in YAP de-UFMylation.
Main Results:
- UFMylation is required for mammalian kidney development.
- Genetic ablation of Ufl1 leads to severe kidney dysplasia, mimicking YAP loss.
- YAP is UFMylated at K76, protecting it from degradation and promoting nuclear translocation.
- UFSP1 is the primary protease for YAP de-UFMylation, and its depletion enhances YAP activity.
Conclusions:
- UFMylation is a critical post-translational mechanism for YAP-dependent transcription during kidney development.
- The study reveals complexity in YAP UFMylation regulation.
- This work implicates a novel etiological pathway for kidney dysplasia.
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