PXD017868-2

PXD017868 is an original dataset announced via ProteomeXchange.

Title	Systematic discovery of Short Linear Motifs decodes calcineurin phosphatase signaling
Description	Short linear motifs (SLiMs) form dynamic protein-protein interactions essential for signaling; however, sequence degeneracy and low binding affinities make them difficult to identify. In this study, we employed multiple, unbiased systematic approaches for SLiM discovery to elucidate the regulatory network of calcineurin (CN), the Ca2+-regulated phosphatase that recognizes LxVP and PxIxIT motifs. In vitro proteome-wide detection of CN-binding peptides, in situ SLiM-dependent proximity labeling, as well as in silico modeling of motif determinants uncovered unanticipated CN interactors, including centrosomal and nuclear pore complex (NPC) proteins – structures where Ca2+ signaling is largely uncharacterized. Here, we show that CN binds to and dephosphorylates NPC proteins (nucleoporins) in vitro and promotes the accumulation of a nuclear transport reporter in HeLa cells. Furthermore, IP/MS analyses on HeLa cells treated with DMSO or the CN inhibitor, Cyclosporin A (CsA), reveal multiple CN-dependent phosphosites on key transport nucleoporins in vivo. Together, these data suggest that CN positively regulates nuclear transport by dephosphorylating key transport nucleoporins. In summary, the CN network assembled here provides a resource to investigate Ca2+ and CN signaling and the demonstrated synergy between experimental and computational methods establishes a blueprint for examining SLiM-based networks.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:16:07.466.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shouling Xu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-03-04 02:05:07	ID requested
1	2020-12-01 23:21:10	announced
⏵ 2	2024-10-22 05:16:08	announced	2024-10-22: Updated project metadata.

Wigington CP, Roy J, Damle NP, Yadav VK, Blikstad C, Resch E, Wong CJ, Mackay DR, Wang JT, Krystkowiak I, Bradburn DA, Tsekitsidou E, Hong SH, Kaderali MA, Xu SL, Stearns T, Gingras AC, Ullman KS, Ivarsson Y, Davey NE, Cyert MS, Systematic Discovery of Short Linear Motifs Decodes Calcineurin Phosphatase Signaling. Mol Cell, 79(2):342-358.e12(2020) [pubmed]

10.1016/j.molcel.2020.06.029;

submitter keyword: Signaling, Calcium, Short Linear Motifs (SLiMs), Nuclear Pore Complex (NPC), Intrinsically Disordered Proteins (IDPs),Phosphatase

shouling xu
contact affiliation	Carnegie Mass Spectrometry Facility at Stanford
contact email	sxu@ciw.edu
lab head
Shouling Xu
contact affiliation	Carnegie Institution at Stanford
contact email	sxu@ciw.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD017868
     1. Label: PRIDE project
     2. Name: Systematic discovery of Short Linear Motifs decodes calcineurin phosphatase signaling