Related Experiment Video

Updated: Jan 10, 2026

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates
09:47

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates

Published on: May 10, 2022

3.0K

UFL1-mediated UFMylation antagonizes IFT88 ubiquitination and degradation to maintain ciliary homeostasis

Runa Wang1, Guizhi Guo1, Renshuai Zhang1

  • 1Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University, Jinan, China.

Cell Death and Differentiation
|November 22, 2025
PubMed

Insights

UFMylation, a protein modification, is vital for ciliary homeostasis. The UFM1 ligase 1 (UFL1) enzyme regulates intraflagellar transport 88 (IFT88) stability, preventing degradation and maintaining ciliary function in various tissues.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • UFMylation, a post-translational modification, is linked to human diseases, but its mechanisms remain unclear.
  • UFM1-specific ligase 1 (UFL1) is the primary enzyme responsible for catalyzing UFMylation.
  • Cilia play crucial roles in cellular function and are implicated in various human disorders.

Purpose of the Study:

  • To investigate the role of UFL1 in ciliary homeostasis.
  • To elucidate the molecular mechanisms by which UFMylation affects ciliary function.
  • To identify novel therapeutic targets for ciliopathies.

Main Methods:

  • Genetic ablation of UFL1 in mice.
  • Analysis of ciliary structure and function in various tissues.
  • Biochemical assays to study protein-protein interactions and post-translational modifications.

Main Results:

  • UFL1 is essential for maintaining ciliary structure and function in mice.
  • UFMylation of intraflagellar transport 88 (IFT88) at lysine 572 prevents its ubiquitination and proteasomal degradation by PJA2.
  • A mutant IFT88 (K572R) shows enhanced stability and rescues UFL1 depletion-induced ciliary defects.

Conclusions:

  • UFMylation of IFT88 is a critical regulatory mechanism for ciliary homeostasis.
  • This study reveals a novel role for UFMylation in preventing IFT88 degradation, impacting ciliary function.
  • The findings provide new insights into the molecular basis of ciliopathies and potential therapeutic strategies.

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