C53 Interacting with UFM1-Protein Ligase 1 Regulates Microtubule Nucleation in Response to ER Stress

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2022 Feb 15

PMID 35159364

Authors

Anastasiya Klebanovych

Stanislav Vinopal

Eduarda Draberova

Vladimira Sladkova

Tetyana Sulimenko

Vadym Sulimenko

Vera Vosecka

Libor Macurek

Agustin Legido

Pavel Draber

Affiliations

Soon will be listed here.

Abstract

ER distribution depends on microtubules, and ER homeostasis disturbance activates the unfolded protein response resulting in ER remodeling. CDK5RAP3 (C53) implicated in various signaling pathways interacts with UFM1-protein ligase 1 (UFL1), which mediates the ufmylation of proteins in response to ER stress. Here we find that UFL1 and C53 associate with γ-tubulin ring complex proteins. Knockout of or in human osteosarcoma cells induces ER stress and boosts centrosomal microtubule nucleation accompanied by γ-tubulin accumulation, microtubule formation, and ER expansion. C53, which is stabilized by UFL1, associates with the centrosome and rescues microtubule nucleation in cells lacking UFL1. Pharmacological induction of ER stress by tunicamycin also leads to increased microtubule nucleation and ER expansion. Furthermore, tunicamycin suppresses the association of C53 with the centrosome. These findings point to a novel mechanism for the relief of ER stress by stimulation of centrosomal microtubule nucleation.

Citing Articles

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A guide to UFMylation, an emerging posttranslational modification.

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Sulimenko V, Draberova E, Draber P Front Cell Dev Biol. 2022; 10:880761.

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