2026-04-29T12:23:02Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/157392024-09-27T08:12:44Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Cuevas-Navarro, Antonio author Rodriguez-Muñoz, Laura author Grego-Bessa, Joaquim author Cheng, Alice author Rauen, Katherine A author Urisman, Anatoly author McCormick, Frank author Jimenez, Gerardo author Castel, Pau author 2022-04-25 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 Lztr1 loss-of-function mutants in both fruit flies and mice and have demonstrated a biochemical preference for their RIT1 orthologs. Moreover, we show that Lztr1 is haplosufficient in mice and that embryonic lethality of the homozygous null allele can be rescued by deletion of Rit1. Overall, our results indicate that, in model organisms, RIT1 orthologs are the preferred substrates of LZTR1. Elife. 2022 Apr 25;11:e76495 10.7554/eLife.76495 2050-084X eLife 35467524 http://hdl.handle.net/20.500.12105/15739 Cross-species analysis of LZTR1 loss-of-function mutants demonstrates dependency to RIT1 orthologs.