PXD013381 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
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 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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD013381
- Label: PRIDE project
- Name: HUVEC endosome LCMS