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An atypical ubiquitin ligase at the heart of neural development and programmed axon degeneration

Neural Regeneration Research 2022年第11期17卷 2347-2350页

作者： Satpal Virdee MRC Protein Phosphorylation and Ubiquitylation Unit University of DundeeScotlandUK

The degeneration of nerve fibres following injury was first described by Augustus Waller over 170 years *** assumed to be a passive process,it is now evident that axons respond to insult via regulated cellular signaling events resulting in their programmed ***-survival and prodegenerative factors have been identified and their regulato ry mechanisms are beginning to *** ubiquitin system has been implicated in the pro-degenerative process and a key component is the ubiquitin E3 ligase mycbp2(also known as PHR1).Ubiquitin E3 ligases are tasked with the transfer of the small protein modifier ubiquitin to substrates and consist of hundreds of *** can be classified as single subunit systems or as multi-subunit *** catalytic domains can also be assigned to three general *** that mycbp2 might not conform to these established formats came to light and it is now clear from biochemical and structural studies that mycbp2 is indeed an outlier in terms of its modus ***,the unconventional way in which mycbp2 transfe rs ubiquitin to substrates has been linked to neurodevelopmental and pro-degenerative ***,we will summarize these research developments relating to the unusual features of mycbp2 and postulate therapeutic strategies that prevent Walle rian *** have exciting potential for providing relief from pathological neuropathies and neurodegenerative diseases.

关键词： chemical biology E3 ligase mycbp2 neurodegeneration progammed axon death structural biology ubiqultin wallerian degeneration

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