2026-05-21T23:11:59Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/157392024-09-27T08:12:44Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
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
funder
NIH - National Cancer Institute (NCI) (Estados Unidos)
funder
Comunidad de Madrid (España)
2023-04-03T12:54:18Z
2023-04-03T12:54:18Z
2022-04-25
Elife. 2022 Apr 25;11:e76495
10.7554/eLife.76495
2050-084X
eLife
35467524
http://hdl.handle.net/20.500.12105/15739
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.
eng
Cross-species analysis of LZTR1 loss-of-function mutants demonstrates dependency to RIT1 orthologs.
journal article
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URL
https://repisalud.isciii.es/bitstreams/f24d0622-d0f1-4773-b851-1abffa0d8d6e/download
File
MD5
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application/pdf
Cross_species analysis of LZTR1 Elife 2022.pdf
URL
https://repisalud.isciii.es/bitstreams/4aeaf6b6-4cca-4a65-b7bd-1b4d3c01496c/download
File
MD5
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text/plain
Cross_species analysis of LZTR1 Elife 2022.pdf.txt