PXD013381

PXD013381 is an original dataset announced via ProteomeXchange.

Title	HUVEC endosome LCMS
Description	Complement 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.
HostingRepository	PRIDE
AnnounceDate	2019-04-09
AnnouncementXML	Submission_2019-05-31_06:05:52.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Caodi Fang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	6520 Quadrupole Time-of-Flight LC/MS

Revision	Datetime	Status	ChangeLog Entry
0	2019-04-05 06:12:28	ID requested
1	2019-04-09 08:54:06	announced
⏵ 2	2019-05-31 06:05:54	announced	Updated publication reference for PubMed record(s): 31113953.

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]

submitter keyword: Rab5 mac

Dan Jane-wit
contact affiliation	Cardiovascular department, Yale University
contact email	dan.jane-wit@yale.edu
lab head
Caodi Fang
contact affiliation	Yale University
contact email	caodi.fang@yale.edu
dataset submitter

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

• PRIDE
  1. PXD013381
     1. Label: PRIDE project
     2. Name: HUVEC endosome LCMS