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Updated: Feb 6, 2026

In Vitro Analysis of E3 Ubiquitin Ligase Function
Published on: May 14, 2021
Regulation of neuronal/axonal degeneration by ZNRF1 ubiquitin ligase
Toshiyuki Araki1, Shuji Wakatsuki1
1Department of Peripheral Nervous System Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8502, Japan.
Abstract:
ZNRF1 is an E3 ubiquitin ligase constitutively expressed in almost all neurons in the central and peripheral nervous systems during development and in adulthood. From this expression profile, the role of ZNRF1 is assumed to be common to many different types of neurons. We have analyzed the roles of ZNRF1-dependent degradation of target proteins in neurons. In mature neurons, ZNRF1 is activated in response to different types of stress that cause neuronal/axonal degeneration, and degrade AKT to activate GSK3B. Here we summarize the subcellular signaling events downstream of GSK3B activation, and their roles in the progression of neuronal/axonal degeneration.
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