PXD006503-3

PXD006503 is an original dataset announced via ProteomeXchange.

Title	NOVEL ROLE OF FATTY ACID SYNTHASE IN ANGIOGENESIS THROUGH MODULATION OF LYSINE MALONYLATION OF MTOR
Description	The role of fatty acid synthesis (FAS) in endothelial cells (ECs) remains incompletely characterized. In this project, we found that silencing of fatty acid synthase (FASN) impedes vessel sprouting by reducing EC proliferation. Moreover, loss of FASN in ECs impaired angiogenesis in vivo, and FASN blockade reduced pathological ocular neovascularization. FASN silencing increased malonyl-CoA levels and immunoblotting of EC lysates for malonylated lysine residues (Kmal) revealed that this led to increased levels of protein malonylation. To identify the nature of some of the malonylated proteins we performed a proteomics screen using an anti-Kmal antibody to enrich Kmal peptides from a tryptic digest of EC lysates, and then analyzed Kmal peptides by LC-MS/MS. In proteomics analysis, we identified malonylation of mTOR at lysine 1218, a poorly characterized post-translational modification. Malonylation of mTOR did not compromise the mTORC1 complex stability or lysosomal membrane localization, but reduced the kinase activity of the complex.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:37:50.202.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD006503
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Evy Timmerman
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Oxidation
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-05-12 02:59:12	ID requested
1	2019-07-08 07:24:36	announced
2	2019-07-08 07:27:29	announced	Updated publication reference for PubMed record(s): 30146486.
⏵ 3	2024-10-22 04:37:58	announced	2024-10-22: Updated project metadata.

Bruning U, Morales-Rodriguez F, Kalucka J, Goveia J, Taverna F, Queiroz KCS, Dubois C, Cantelmo AR, Chen R, Loroch S, Timmerman E, Caixeta V, Bloch K, Conradi LC, Treps L, Staes A, Gevaert K, Tee A, Dewerchin M, Semenkovich CF, Impens F, Schilling B, Verdin E, Swinnen JV, Meier JL, Kulkarni RA, Sickmann A, Ghesqui, è, re B, Schoonjans L, Li X, Mazzone M, Carmeliet P, Impairment of Angiogenesis by Fatty Acid Synthase Inhibition Involves mTOR Malonylation. Cell Metab, 28(6):866-880.e15(2018) [pubmed]

10.1016/j.cmet.2018.07.019;

10.6019/PXD006503;

curator keyword: Biological

submitter keyword: protein malonylation, fatty acid synthesis,endothelial cell metabolism

Carmeliet Peter
contact affiliation	(1) Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, Department of Oncology, University of Leuven, Leuven, B-3000, Belgium; (2) Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, VIB, Leuven, B-3000, Belgium
contact email	peter.carmeliet@kuleuven.vib.be
lab head
Evy Timmerman
contact affiliation	Ghent University - VIB
contact email	evy.timmerman@vib-ugent.be
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/2019/07/PXD006503

PRIDE project URI

• PRIDE
  1. PXD006503
     1. Label: PRIDE project
     2. Name: NOVEL ROLE OF FATTY ACID SYNTHASE IN ANGIOGENESIS THROUGH MODULATION OF LYSINE MALONYLATION OF MTOR