C53 interacting with UFM1-protein ligase 1 regulates microtubule nucleation in response to ER stress

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 UFL1 or C53 in human osteosarcoma cells induces ER stress, centrosomal microtubule nucleation accompanied by γ-tubulin accumulation and ER expansion. C53, whose protein level is modulated 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.

Tachykinin-related peptides modulate immune-gene expression in the mealworm beetle Tenebrio molitor L.

“…In the 10 –6 M Tenmo-TRP-7 treatment, we observed the overexpression of 26S protease regulatory subunit 4 and an apoptotic chromatin condensation inducer in the nucleus, which are likely involved in regulating apoptosis 98 , 99 . The genes for CCR4-NOT transcription complex subunit 6-like protein and E3 UFM1-protein ligase 1 homolog, which is related to the DNA damage response 100 , 101 , were downregulated. The gene for histone-arginine methyltransferase CARMER was also downregulated.…”