Genetic determinants of proteostatic KRAS regulation
Modulation of RAS GTPase protein abundance by the LZTR1 Cullin 3 (CUL3) E3 ubiquitin ligase complex (CRL3-LZTR1) has emerged as an important control layer of the RAS and MAPK pathway. However, despite its importance, the specific cellular requirements governing CRL3-LZTR1- mediated RAS regulation remained unclear. Here, we used a fluorescence-activated cell sorting (FACS)-based CRISPR knockout screen in endogenously affinity-tagged KRAS cells, to map the genetic requirements for proteostatic KRAS regulation on a genome-wide scale.