Shigella entry unveils a calcium/calpain-dependent mechanism for inhibiting sumoylation.

Abstract:

: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.

journal_name

Elife

journal_title

eLife

authors

Lapaquette P,Fritah S,Lhocine N,Andrieux A,Nigro G,Mounier J,Sansonetti P,Dejean A

doi

10.7554/eLife.27444

subject

Has Abstract

pub_date

2017-12-12 00:00:00

issn

2050-084X

pii

27444

journal_volume

6

pub_type

杂志文章

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