Screening of gene function in cell intoxication by CNF1 links Sec61 translocon to Rac1 GTPase activity.

ABSTRACT: The CNF1 toxin from extraintestinal pathogenic Escherichia coli (ExPEC) deamidates glutamine 61 of Rac1 small GTPase, as well as its equivalents in RhoA and Cdc42 into glutamic acid. This post-translational modification of Rho proteins abrogates the hydrolysis of GTP into GDP, thereby enhancing signal transduction. Meanwhile, the sustained GTP-loading of Rac1 Q61E sensitizes it to ubiquitin-mediated proteasomal degradation catalyzed by the HACE1 E3 ligase rate-limiting factor, leading to a cellular depletion of Rac1 over time. We report data from a quantitative genome-wide screen of siRNAs inhibiting CNF1-mediated cellular depletion of Rac1 in primary human cells. As best hits, we identified a group of three siRNAs targeting the Sec61A1 subunit of the Sec61 translocon, as well as HA

SUBMITTER: Paillares E 

PROVIDER: S-EPMC12607883 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature