⮝ Full datasets listing

PXD013381

PXD013381 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleHUVEC endosome LCMS
DescriptionComplement promotes vascular inflammation in transplant organ rejection and connective tissue diseases. Here we identify ZFYVE21 as a complement-induced Rab5 effector that regulates pro-inflammatory non-canonical NF-B signaling in endothelial cells (EC). In response to membrane attack complexes (MAC), ZFYVE21 is post-translationally stabilized via recruitment to MAC+Rab5+ endosomes in a Rab5- and PI(3)P-dependent manner. ZFYVE21 promotes SMURF2-mediated polyubiquitinylation and proteasome-dependent degradation of endosome-associated PTEN to induce vesicular enrichment of PI(3,4,5)P3 and sequential recruitment of activated Akt and NF-B-inducing kinase (NIK). Pharmacologic alteration of the phosphoinositide content of MAC+Rab5+ endosomes with miltefosine reduces ZFYVE21 induction, EC activation, as well as allograft vasculopathy in a humanized mouse model. ZFYVE21 induction distinctly occurs in response to MAC- but not ligand-induced non-canonical NF-B and is a biomarker for complement-mediated endothelial signaling in human renal and synovial tissues. Our data identifies ZFYVE21 as a novel Rab5 effector, defines a Rab5-ZFYVE21-SMURF2-pAkt axis by which it mediates EC activation, and demonstrates a role for this pathway as a drug target and biomarker for complement-mediated pathologies.
HostingRepositoryPRIDE
AnnounceDate2019-04-09
AnnouncementXMLSubmission_2019-05-31_06:05:52.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterCaodi Fang
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
Instrument6520 Quadrupole Time-of-Flight LC/MS
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-04-05 06:12:28ID requested
12019-04-09 08:54:06announced
22019-05-31 06:05:54announcedUpdated publication reference for PubMed record(s): 31113953.
Publication List
Fang C, Manes TD, Liu L, Liu K, Qin L, Li G, Tobiasova Z, Kirkiles-Smith NC, Patel M, Merola J, Fu W, Liu R, Xie C, Tietjen GT, Nigrovic PA, Tellides G, Pober JS, Jane-Wit D, B via phosphoinosotide remodeling of endosomes. Nat Commun, 10(1):2247(2019) [pubmed]
Keyword List
submitter keyword: Rab5 mac
Contact List
Dan Jane-wit
contact affiliationCardiovascular department, Yale University
contact emaildan.jane-wit@yale.edu
lab head
Caodi Fang
contact affiliationYale University
contact emailcaodi.fang@yale.edu
dataset submitter
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/04/PXD013381
PRIDE project URI
Repository Record List
[ + ]