Akademik Veri Yönetim Sistemi
International Neuroscience Conference 2025, Tbilisi, Gürcistan, 29 - 30 Kasım 2025, ss.298, (Özet Bildiri)
Abstract
Post-translational protein arginylation represents a key regulatory
mechanism influencing numerous physiological pathways in cells. Nterminal
arginylation is primarily linked to the degradation of proteins
or protein fragments within the framework of the N-end rule pathway.
Arginyltransferase (ATE1) has been shown to modify the N-termini of
proteolytic fragments generated by various enzymes, including
calcium-activated caspases, separases, metalloproteases, and calpains.
Post-translational arginylation, catalyzed by ATE1, directly regulates
the metabolism and function of numerous protein substrates, including
protease-derived polypeptides. This modification can significantly
influence protein stability, localization, and activity. Post-translational
arginylation by ATE1 regulates protein metabolism and function, often
targeting protease-derived polypeptides. Studies showed that Ate1 acts
as a key regulator of oligodendrocyte differentiation and myelination by
modulating the actin cytoskeleton. Ate1-mediated arginylation
influences multiple cellular and developmental processes in
oligodendrocytes and may serve as a potential therapeutic target to
enhance axonal metabolic support during recovery from demyelinating
disorders. Although only a fraction of proteins is arginylated, this
modification critically influences their stability, localization, and cellular
roles. In the brain and spinal cord, several ER-resident proteins, such as
calreticulin and BiP (GRP78), become ATE1 substrates after stressinduced
retro-translocation to the cytosol. Arginylated BiP is directed to
autophagosomes for degradation, while arginylated calreticulin
relocates to stress granules and the plasma membrane, adopting new
functions. The fate of arginylated proteins depends on their subcellular
localization and cellular conditions, with some avoiding proteasomal
degradation through protein interactions. Overall, ATE1-mediated
arginylation emerges as a versatile regulatory mechanism affecting
neuronal proteostasis and neurodegenerative pathology.