Figure 2.

Signaling pathways of Shiga toxin (Stx), Cytolethal Distending Toxin (CDT) and Subtilase AB (SubAB). Activated and inactivated proteins are colored in green and red, respectively. Arrow colors match catalytic moieties of toxins. Dashed arrows are drawn when the precise mechanism is unknown. (i) Shiga toxin (Stx) binds to the cell-surface receptor Gb3 through the pentameric B subunit (dark red), followed by an internalization of the enzymatic A subunit (purple). Stx induces irreversible DNA damage that activates ATF3 and GADDs proteins, leading to cell cycle arrest in the G2 phase. Stx also induces CdkN3 that results in cell cycle arrest in the G2 phase. (ii) Cytolethal Distending Toxin (CDT) binds to an unknown cell membrane receptor through CdtA and CdtC (blue), leading to an enzymatic CdtB (yellow) internalization. CDT causes DNA damage that leads to the activation of ATM, followed by Cdc25C sequestration by CHK2. Consequently, Cdc25C is not free to bind CDK1, leading to its inhibition and, ultimately, to arrest of cells in the G2 phase. DNA damage caused by CDT also activates p53 and p21^Cip1, causing CDK2, and CycE inactivation and cell cycle arrest in the G1 phase. (iii) Subtilase AB binds integrins at the cell surface with the pentameric B subunit (orange) followed by the entrance of the enzymatic A subunit (pink). SubAB cleaves the chaperone BiP that activates PERK and eIF2α, leading to a translation inhibition. Finally, cyclin D1 is down-regulated and causes the arrest of cells in the G1 phase.