Staes A

References (3)

Title : Impairment of Angiogenesis by Fatty Acid Synthase Inhibition Involves mTOR Malonylation - Bruning_2018_Cell.Metab_28_866
Author(s) : 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 , Ghesquiere B , Schoonjans L , Li X , Mazzone M , Carmeliet P
Ref : Cell Metab , 28 :866 , 2018
Abstract : The role of fatty acid synthesis in endothelial cells (ECs) remains incompletely characterized. We report that fatty acid synthase knockdown (FASN(KD)) in ECs impedes vessel sprouting by reducing proliferation. Endothelial loss of FASN impaired angiogenesis insvivo, while FASN blockade reduced pathological ocular neovascularization, at >10-fold lower doses than used for anti-cancer treatment. Impaired angiogenesis was not due to energy stress, redox imbalance, or palmitate depletion. Rather, FASN(KD) elevated malonyl-CoA levels, causing malonylation (a post-translational modification) of mTOR at lysine 1218 (K1218). mTOR K-1218 malonylation impaired mTOR complex 1 (mTORC1) kinase activity, thereby reducing phosphorylation of downstream targets (p70S6K/4EBP1). Silencing acetyl-CoA carboxylase 1 (an enzyme producing malonyl-CoA) normalized malonyl-CoA levels and reactivated mTOR in FASN(KD) ECs. Mutagenesis unveiled the importance of mTOR K1218 malonylation for angiogenesis. This study unveils a novel role of FASN in metabolite signaling that contributes to explaining the anti-angiogenic effect of FASN blockade.
ESTHER : Bruning_2018_Cell.Metab_28_866
PubMedSearch : Bruning_2018_Cell.Metab_28_866
PubMedID: 30146486

Title : The Response of the Root Proteome to the Synthetic Strigolactone GR24 in Arabidopsis - Walton_2016_Mol.Cell.Proteomics_15_2744
Author(s) : Walton A , Stes E , Goeminne G , Braem L , Vuylsteke M , Matthys C , De Cuyper C , Staes A , Vandenbussche J , Boyer FD , Vanholme R , Fromentin J , Boerjan W , Gevaert K , Goormachtig S
Ref : Mol Cell Proteomics , 15 :2744 , 2016
Abstract : Strigolactones are plant metabolites that act as phytohormones and rhizosphere signals. Whereas most research on unraveling the action mechanisms of strigolactones is focused on plant shoots, we investigated proteome adaptation during strigolactone signaling in the roots of Arabidopsis thaliana. Through large-scale, time-resolved, and quantitative proteomics, the impact of the strigolactone analog rac-GR24 was elucidated on the root proteome of the wild type and the signaling mutant more axillary growth 2 (max2). Our study revealed a clear MAX2-dependent rac-GR24 response: an increase in abundance of enzymes involved in flavonol biosynthesis, which was reduced in the max2-1 mutant. Mass spectrometry-driven metabolite profiling and thin-layer chromatography experiments demonstrated that these changes in protein expression lead to the accumulation of specific flavonols. Moreover, quantitative RT-PCR revealed that the flavonol-related protein expression profile was caused by rac-GR24-induced changes in transcript levels of the corresponding genes. This induction of flavonol production was shown to be activated by the two pure enantiomers that together make up rac-GR24. Finally, our data provide much needed clues concerning the multiple roles played by MAX2 in the roots and a comprehensive view of the rac-GR24-induced response in the root proteome.
ESTHER : Walton_2016_Mol.Cell.Proteomics_15_2744
PubMedSearch : Walton_2016_Mol.Cell.Proteomics_15_2744
PubMedID: 27317401

Title : Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides - Gevaert_2003_Nat.Biotechnol_21_566
Author(s) : Gevaert K , Goethals M , Martens L , Van Damme J , Staes A , Thomas GR , Vandekerckhove J
Ref : Nat Biotechnol , 21 :566 , 2003
Abstract : Current non-gel techniques for analyzing proteomes rely heavily on mass spectrometric analysis of enzymatically digested protein mixtures. Prior to analysis, a highly complex peptide mixture is either separated on a multidimensional chromatographic system or it is first reduced in complexity by isolating sets of representative peptides. Recently, we developed a peptide isolation procedure based on diagonal electrophoresis and diagonal chromatography. We call it combined fractional diagonal chromatography (COFRADIC). In previous experiments, we used COFRADIC to identify more than 800 Escherichia coli proteins by tandem mass spectrometric (MS/MS) analysis of isolated methionine-containing peptides. Here, we describe a diagonal method to isolate N-terminal peptides. This reduces the complexity of the peptide sample, because each protein has one N terminus and is thus represented by only one peptide. In this new procedure, free amino groups in proteins are first blocked by acetylation and then digested with trypsin. After reverse-phase (RP) chromatographic fractionation of the generated peptide mixture, internal peptides are blocked using 2,4,6-trinitrobenzenesulfonic acid (TNBS); they display a strong hydrophobic shift and therefore segregate from the unaltered N-terminal peptides during a second identical separation step. N-terminal peptides can thereby be specifically collected for further liquid chromatography (LC)-MS/MS analysis. Omitting the acetylation step results in the isolation of non-lysine-containing N-terminal peptides from in vivo blocked proteins.
ESTHER : Gevaert_2003_Nat.Biotechnol_21_566
PubMedSearch : Gevaert_2003_Nat.Biotechnol_21_566
PubMedID: 12665801
Gene_locus related to this paper: human-ABHD16A