Comment regarding “dominant-negative phenotype” of the mutant with disrupted RING Finger domain in E3 Ligase (Reference: eLife 2022;11:e71928).

Alex Sobko, PhD

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Mar 29, 2022

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Very interesting mechanism to account for the phenotype of the mutant disrupting RING Finger E3 Ligase Mib1! A mutant E3 Ligase binds, traps ubiquitin conjugation substrate proteins but fails to ubiqutinate them, functions like a “molecular sponge” — common feature of so-called “dominant-negative mutants”. There are other paradigms in Dev Biology (besides Notch/Delta and Wnt Signaling), in which such phenomenon has been noted — for example, Sobko A, Ma H, Firtel R, Dev Cell, 2002. It is very exciting that the authors engineered RING Finger mutant using CRISPR-Cas9 Gene Editing. Recently, I have proposed to do the same in other biological contexts — Sobko A. “CRISPR-Cas9 gene editing approach to study the functions of post-translational protein modifications in MAP Kinase Kinases DdMEK1-MAP2K1/2.” CSHL (Virtual) Conference — Genome Engineering: CRISPR Frontiers, August 2021. ePoster and video- presentation.