Dataset Information

Identification of novel SHARPIN binders

ABSTRACT: Sharpin, a multifunctional adaptor protein with oncogenic properties, regulates several signalling pathways. For example, Sharpin enhances signal-induced NF-κB signalling as part of the linear ubiquitin assembly complex (LUBAC) and inhibits integrins, the T cell receptor, caspase1 and PTEN. However, despite recent insights into Sharpin and LUBAC function, a systematic approach to identify signalling pathways regulated by Sharpin has not been reported. Here, we present the first ‘Sharpin interactome’, which identifies a large amount of novel potential Sharpin interactors. These data suggest that Sharpin and LUBAC might regulate a larger number of biological processes than previously identified, such as endosomal trafficking, RNA processing, metabolism and cytoskeleton regulation. Importantly, using the Sharpin interactome we have identified a novel role for Sharpin in lamellipodium formation. We demonstrate that Sharpin interacts with the Arp2/3 complex, a protein complex that catalyses actin filament branching, and that Sharpin and Arp2/3 colocalize in lamellipodia. We identified the Arp2/3-binding site in Sharpin and demonstrate using a specific Arp2/3-binding deficient mutant that the Sharpin-Arp2/3 interaction promotes lamellipodia formation in a LUBAC-independent fashion.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

SUBMITTER: Guillaume Jacquemet

LAB HEAD: Jeroen Pouwels

PROVIDER: PXD004734 | Pride | 2017-08-11

REPOSITORIES: Pride

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The Sharpin interactome reveals a role for Sharpin in lamellipodium formation via the Arp2/3 complex.

Khan Meraj H MH Salomaa Siiri I SI Jacquemet Guillaume G Butt Umar U Miihkinen Mitro M Deguchi Takahiro T Kremneva Elena E Lappalainen Pekka P Humphries Martin J MJ Pouwels Jeroen J

Journal of cell science 20170803 18

Sharpin, a multifunctional adaptor protein, regulates several signalling pathways. For example, Sharpin enhances signal-induced NF-κB signalling as part of the linear ubiquitin assembly complex (LUBAC) and inhibits integrins, the T cell receptor, caspase 1 and PTEN. However, despite recent insights into Sharpin and LUBAC function, a systematic approach to identify the signalling pathways regulated by Sharpin has not been reported. Here, we present the first 'Sharpin interactome', which identifie ...[more]

PMID: 28775156

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