{Reference Type}: Journal Article
{Title}: The Shigella kinase effector OspG modulates host ubiquitin signaling to escape septin-cage entrapment.
{Author}: Xian W;Fu J;Zhang Q;Li C;Zhao YB;Tang Z;Yuan Y;Wang Y;Zhou Y;Brzoic PS;Zheng N;Ouyang S;Luo ZQ;Liu X;
{Journal}: Nat Commun
{Volume}: 15
{Issue}: 1
{Year}: 2024 May 8
{Factor}: 17.694
{DOI}: 10.1038/s41467-024-48205-4
{Abstract}: Shigella flexneri is a Gram-negative bacterium causing severe bloody dysentery. Its pathogenesis is largely dictated by a plasmid-encoded type III secretion system (T3SS) and its associated effectors. Among these, the effector OspG has been shown to bind to the ubiquitin conjugation machinery (E2~Ub) to activate its kinase activity. However, the cellular targets of OspG remain elusive despite years of extensive efforts. Here we show by unbiased phosphoproteomics that a major target of OspG is CAND1, a regulatory protein controlling the assembly of cullin-RING ubiquitin ligases (CRLs). CAND1 phosphorylation weakens its interaction with cullins, which is expected to impact a large panel of CRL E3s. Indeed, global ubiquitome profiling reveals marked changes in the ubiquitination landscape when OspG is introduced. Notably, OspG promotes ubiquitination of a class of cytoskeletal proteins called septins, thereby inhibiting formation of cage-like structures encircling cytosolic bacteria. Overall, we demonstrate that pathogens have evolved an elaborate strategy to modulate host ubiquitin signaling to evade septin-cage entrapment.