Cross-species Analysis of LZTR1 Loss-of-function Mutants Demonstrates Dependency to RIT1 Orthologs

Overview

Journal Elife

Specialty Biology

Date 2022 Apr 25

PMID 35467524

Authors

Antonio Cuevas-Navarro

Laura Rodriguez-Munoz

Joaquim Grego-Bessa

Alice Cheng

Katherine A Rauen

Anatoly Urisman

Frank McCormick

Gerardo Jimenez

Pau Castel

Affiliations

Soon will be listed here.

Abstract

RAS GTPases are highly conserved proteins involved in the regulation of mitogenic signaling. We have previously described a novel Cullin 3 RING E3 ubiquitin ligase complex formed by the substrate adaptor protein LZTR1 that binds, ubiquitinates, and promotes proteasomal degradation of the RAS GTPase RIT1. In addition, others have described that this complex is also responsible for the ubiquitination of classical RAS GTPases. Here, we have analyzed the phenotypes of loss-of-function mutants in both fruit flies and mice and have demonstrated a biochemical preference for their RIT1 orthologs. Moreover, we show that is haplosufficient in mice and that embryonic lethality of the homozygous null allele can be rescued by deletion of . Overall, our results indicate that, in model organisms, RIT1 orthologs are the preferred substrates of LZTR1.

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