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

eLife | 2017

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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GE Healthcare (tool)

RRID:SCR_000004

A commercial antibody supplier and provider of various services.

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ATCC (tool)

RRID:SCR_001672

Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

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Clustal W2 (tool)

RRID:SCR_002909

THIS RESOURCE IS NO LONGER IN SERVICE, documented on January 19, 2022. Command line version of multiple sequence alignment program Clustal for DNA or proteins. Alignment is progressive and considers sequence redundancy. No longer being maintained. Please consider using Clustal Omega instead which accepts nucleic acid or protein sequences in multiple sequence formats NBRF/PIR, EMBL/UniProt, Pearson (FASTA), GDE, ALN/ClustalW, GCG/MSF, RSF.

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Cell Signaling Technology (tool)

RRID:SCR_004431

Privately held company that develops and produces antibodies, ELISA kits, ChIP kits, proteomic kits, and other related reagents used to study cell signaling pathways that impact human health.

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DSHB (tool)

RRID:SCR_013527

An antibody supplier which banks and distributes hybridomas and monoclonal antibodies for use in research. The bank includes antibodies against targets such as GFP, transcription factors, stem cells, and human.

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Sumo 2+3 antibody [8A2] (antibody)

RRID:AB_1658424

This monoclonal targets Human Sumo 2 / 3

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UBA2 (D15C11) Rabbit mAb (antibody)

RRID:AB_10889561

This monoclonal targets UBA2 (D15C11) Rabbit mAb

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Phalloidin-TRITC (antibody)

RRID:AB_2315148

This unknown targets

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RhoA (67B9) Rabbit mAb (antibody)

RRID:AB_10693922

This monoclonal targets RhoA (67B9) Rabbit mAb

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Anti-Rac1, clone 23A8 (antibody)

RRID:AB_309712

This monoclonal targets Rac1 clone 23A8

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Sumo 1 antibody [Y299] (antibody)

RRID:AB_778173

This monoclonal targets Sumo 1

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UBC-9 (antibody)

RRID:AB_1267373

This monoclonal targets Ube2i

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Anti-RhoGDI (antibody)

RRID:AB_310229

This polyclonal targets RhoGDI

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SAE1 antibody (antibody)

RRID:AB_10681015

This polyclonal targets SAE1 antibody

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HT-1080 (cell line)

RRID:CVCL_0317

Cell line HT-1080 is a Cancer cell line with a species of origin Homo sapiens (Human)

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HeLa (cell line)

RRID:CVCL_0030

Cell line HeLa is a Cancer cell line with a species of origin Homo sapiens

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SAE1 antibody (antibody)

RRID:AB_10681015

This polyclonal targets SAE1 antibody

View all literature mentions

Sumo 1 antibody [Y299] (antibody)

RRID:AB_778173

This monoclonal targets Sumo 1

View all literature mentions

HT-1080 (cell line)

RRID:CVCL_0317

Cell line HT-1080 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

HeLa (cell line)

RRID:CVCL_0030

Cell line HeLa is a Cancer cell line with a species of origin Homo sapiens

View all literature mentions

Sumo 2+3 antibody [8A2] (antibody)

RRID:AB_1658424

This monoclonal targets Human Sumo 2 / 3

View all literature mentions

UBC-9 (antibody)

RRID:AB_1267373

This monoclonal targets Ube2i

View all literature mentions

UBA2 (D15C11) Rabbit mAb (antibody)

RRID:AB_10889561

This monoclonal targets UBA2 (D15C11) Rabbit mAb

View all literature mentions

HeLa (cell line)

RRID:CVCL_0030

Cell line HeLa is a Cancer cell line with a species of origin Homo sapiens

View all literature mentions

Anti-RhoGDI (antibody)

RRID:AB_310229

This polyclonal targets RhoGDI

View all literature mentions

HT-1080 (cell line)

RRID:CVCL_0317

Cell line HT-1080 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

RhoA (67B9) Rabbit mAb (antibody)

RRID:AB_10693922

This monoclonal targets RhoA (67B9) Rabbit mAb

View all literature mentions

Sumo 1 antibody [Y299] (antibody)

RRID:AB_778173

This monoclonal targets Sumo 1

View all literature mentions

UBC-9 (antibody)

RRID:AB_1267373

This monoclonal targets Ube2i

View all literature mentions

Anti-Rac1, clone 23A8 (antibody)

RRID:AB_309712

This monoclonal targets Rac1 clone 23A8

View all literature mentions

Phalloidin-TRITC (antibody)

RRID:AB_2315148

This unknown targets

View all literature mentions

Sumo 2+3 antibody [8A2] (antibody)

RRID:AB_1658424

This monoclonal targets Human Sumo 2 / 3

View all literature mentions

SAE1 antibody (antibody)

RRID:AB_10681015

This polyclonal targets SAE1 antibody

View all literature mentions

Phalloidin-TRITC (antibody)

RRID:AB_2315148

This unknown targets

View all literature mentions

Anti-RhoGDI (antibody)

RRID:AB_310229

This polyclonal targets RhoGDI

View all literature mentions

UBA2 (D15C11) Rabbit mAb (antibody)

RRID:AB_10889561

This monoclonal targets UBA2 (D15C11) Rabbit mAb

View all literature mentions

RhoA (67B9) Rabbit mAb (antibody)

RRID:AB_10693922

This monoclonal targets RhoA (67B9) Rabbit mAb

View all literature mentions

Anti-Rac1, clone 23A8 (antibody)

RRID:AB_309712

This monoclonal targets Rac1 clone 23A8

View all literature mentions