Disruption of the sumoylation/desumoylation equilibrium is associated with several disease states such as cancer and infections, however the mechanisms regulating the global SUMO balance remain poorly defined. Here, we show that infection by Shigella flexneri, the causative agent of human bacillary dysentery, switches off host sumoylation during epithelial cell infection in vitro and in vivo and that this effect is mainly mediated by a calcium/calpain-induced cleavage of the SUMO E1 enzyme SAE2, thus leading to sumoylation inhibition. Furthermore, we describe a mechanism by which Shigella promotes its own invasion by altering the sumoylation state of RhoGDIα, a master negative regulator of RhoGTPase activity and actin polymerization. Together, our data suggest that SUMO modification is essential to restrain pathogenic bacterial entry by limiting cytoskeletal rearrangement induced by bacterial effectors. Moreover, these findings identify calcium-activated calpains as powerful modulators of cellular sumoylation levels with potentially broad implications in several physiological and pathological situations.
Pubmed ID: 29231810 RIS Download
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View all literature mentionsThis monoclonal targets Human Sumo 2 / 3
View all literature mentionsThis polyclonal targets Cast
View all literature mentionsThis monoclonal targets alpha-Tubulin (DM1A) Mouse mAb
View all literature mentionsThis monoclonal targets UBA2 (D15C11) Rabbit mAb
View all literature mentionsThis monoclonal targets Calpain small subunit (??- or m-Calpain), small subunit
View all literature mentionsThis monoclonal targets Human RANGAP1
View all literature mentionsThis polyclonal targets SAE2 / UBA2
View all literature mentionsThis monoclonal targets RhoA (67B9) Rabbit mAb
View all literature mentionsThis monoclonal targets Rac1 clone 23A8
View all literature mentionsThis monoclonal targets Sumo 1
View all literature mentionsThis polyclonal targets SAE1 antibody
View all literature mentionsThis monoclonal targets SUMO1, aa 57-67
View all literature mentionsCell line HT-1080 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsThis polyclonal targets SAE1 antibody
View all literature mentionsThis polyclonal targets SAE2 / UBA2
View all literature mentionsThis monoclonal targets Sumo 1
View all literature mentionsCell line HT-1080 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsThis polyclonal targets Cast
View all literature mentionsThis monoclonal targets SUMO1, aa 57-67
View all literature mentionsThis monoclonal targets Human Sumo 2 / 3
View all literature mentionsThis monoclonal targets UBA2 (D15C11) Rabbit mAb
View all literature mentionsThis monoclonal targets Calpain small subunit (??- or m-Calpain), small subunit
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsThis monoclonal targets Human RANGAP1
View all literature mentionsCell line HT-1080 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets RhoA (67B9) Rabbit mAb
View all literature mentionsThis monoclonal targets alpha-Tubulin (DM1A) Mouse mAb
View all literature mentionsThis polyclonal targets Cast
View all literature mentionsThis monoclonal targets Human RANGAP1
View all literature mentionsThis monoclonal targets Sumo 1
View all literature mentionsThis monoclonal targets Rac1 clone 23A8
View all literature mentionsThis polyclonal targets SAE2 / UBA2
View all literature mentionsThis monoclonal targets Human Sumo 2 / 3
View all literature mentionsThis polyclonal targets SAE1 antibody
View all literature mentionsThis monoclonal targets SUMO1, aa 57-67
View all literature mentionsThis monoclonal targets Calpain small subunit (??- or m-Calpain), small subunit
View all literature mentionsThis monoclonal targets alpha-Tubulin (DM1A) Mouse mAb
View all literature mentionsThis monoclonal targets UBA2 (D15C11) Rabbit mAb
View all literature mentionsThis monoclonal targets RhoA (67B9) Rabbit mAb
View all literature mentionsThis monoclonal targets Rac1 clone 23A8
View all literature mentions