Ubiquitin fold modifier 1 (UFM1) and its target UFBP1 protect pancreatic beta cells from ER stress-induced apoptosis

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

Published on: May 10, 2022

Katleen Lemaire1, Rodrigo F Moura, Mikaela Granvik

  • 1Gene Expression Unit, Department Molecular Cell Biology, KatholiekeUniversiteit Leuven, Leuven, Belgium. katleen.lemaire@med.kuleuven.be

Plos One
|April 16, 2011
PubMed

Insights

The UFM1-UFBP1 conjugation pathway is crucial for preventing apoptosis in pancreatic beta cells during endoplasmic reticulum stress. This finding highlights a key mechanism for maintaining secretory cell function.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The ubiquitin-like modifier UFM1 (ubiquitin fold modifier 1) is part of a unique post-translational modification system.
  • While the UFM1 conjugation cascade is known, its precise biological roles, particularly in secretory cells, remain largely undefined.

Purpose of the Study:

  • To investigate the biological function of UFM1 and its interacting partners in the context of endoplasmic reticulum (ER) stress.
  • To elucidate the role of UFM1-UFBP1 conjugation in cellular responses to ER stress in pancreatic beta cells.

Main Methods:

  • Co-immunoprecipitation and co-localization studies to identify UFM1 interacting proteins.
  • siRNA-mediated knockdown of UFM1, UFBP1, and UFL1 in INS-1E cells.
  • Assessment of apoptosis induction under ER stress conditions following gene silencing.

Main Results:

  • Identified UFBP1 (UFM1-binding protein 1) and CDK5RAP3 as novel interacting partners of UFM1.
  • Demonstrated that UFM1 and UFBP1 co-localize in the ER, dependent on UFBP1.
  • Showed that knockdown of UFM1 or UFBP1 exacerbates apoptosis induced by ER stress in INS-1E cells.

Conclusions:

  • The UFM1-UFBP1 conjugation pathway is essential for protecting protein secretory cells, such as pancreatic beta cells, from ER stress-induced apoptosis.
  • UFM1-UFBP1 conjugation plays a critical role in maintaining cellular homeostasis under conditions of proteotoxic stress.

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