PXD004734

PXD004734 is an original dataset announced via ProteomeXchange.

Title	Identification of novel SHARPIN binders
Description	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.
HostingRepository	PRIDE
AnnounceDate	2017-08-11
AnnouncementXML	Submission_2017-08-11_00:30:21.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD004734
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Guillaume Jacquemet
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2016-08-08 09:15:28	ID requested
⏵ 1	2017-08-11 00:30:22	announced

Khan MH, Salomaa SI, Jacquemet G, Butt U, Miihkinen M, Deguchi T, Kremneva E, Lappalainen P, Humphries MJ, Pouwels J, The Sharpin interactome reveals a role for Sharpin in lamellipodium formation via the Arp2/3 complex. J Cell Sci, 130(18):3094-3107(2017) [pubmed]

curator keyword: Biological

submitter keyword: SHARPIN, GFP pull-down, human

Jeroen Pouwels
contact affiliation	Turku Centre for Biotechnology, University of Turku, Turku, Finland,
contact email	jpouwels@btk.fi
lab head
Guillaume Jacquemet
contact affiliation	University of Turku
contact email	guillaume.jacquemet@btk.fi
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD004734
     1. Label: PRIDE project
     2. Name: Identification of novel SHARPIN binders