PMID:18005237

Citation	Morinaga, N, Yahiro, K, Matsuura, G, Moss, J and Noda, M (2008) Subtilase cytotoxin, produced by Shiga-toxigenic Escherichia coli, transiently inhibits protein synthesis of Vero cells via degradation of BiP and induces cell cycle arrest at G1 by downregulation of cyclin D1. Cell. Microbiol. 10:921-9
Abstract	Subtilase cytotoxin (SubAB) is a AB(5) type toxin produced by Shiga-toxigenic Escherichia coli, which exhibits cytotoxicity to Vero cells. SubAB B subunit binds to toxin receptors on the cell surface, whereas the A subunit is a subtilase-like serine protease that specifically cleaves chaperone BiP/Grp78. As noted previously, SubAB caused inhibition of protein synthesis. We now show that the inhibition of protein synthesis was transient and occurred as a result of ER stress induced by cleavage of BiP; it was closely associated with phosphorylation of double-stranded RNA-activated protein kinase-like ER kinase (PERK) and eukaryotic initiation factor-2alpha (eIF2alpha). The phosphorylation of PERK and eIF2alpha was maximal at 30-60 min and then returned to the control level. Protein synthesis after treatment of cells with SubAB was suppressed for 2 h and recovered, followed by induction of stress-inducible C/EBP-homologous protein (CHOP). BiP degradation continued, however, even after protein synthesis recovered. SubAB-treated cells showed cell cycle arrest in G1 phase, which may result from cyclin D1 downregulation caused by both SubAB-induced translational inhibition and continuous prolonged proteasomal degradation.
Links	PubMed PMC3021990 Online version:10.1111/j.1462-5822.2007.01094.x
Keywords	Animals; Blotting, Western; Cell Cycle/drug effects; Cercopithecus aethiops; Cyclin D1/genetics; Cyclin D1/metabolism; Escherichia coli Proteins/pharmacology; Flow Cytometry; G1 Phase/drug effects; Heat-Shock Proteins/metabolism; Molecular Chaperones/metabolism; Protein Biosynthesis/drug effects; Reverse Transcriptase Polymerase Chain Reaction; Shiga-Toxigenic Escherichia coli/enzymology; Subtilisins/pharmacology; Vero Cells
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
ECOLX:G9IBF5		GO:0007050: cell cycle arrest	ECO:0000314:		P		Figure 5 shows a western blot looking at the effect SubAB has on the levels of cyclin D1, cyclin D3, Cdk4, and Cdk6. This experiment was done to examine the underlying cause of cell cycle arrest. A significant downregulation of cyclin D1 occurred between 30 and 60 minutes after exposure to SubAB. Cyclin D is a G1 cyclin and the downregulation of cyclin D1 led to arrest in G1 of the cell cycle.	complete CACAO 4219

References

See Help:References for how to manage references in GONUTS.