Bruning, Ulrike; Morales-Rodriguez, Francisco; Kalucka, Joanna; Goveia, Jermaine; Taverna, Federico; Queiroz, Karla C. S.; Dubois, Charlotte; Cantelmo, Anna Rita; Chen, Rongyuan; Loroch, Stefan; Timmerman, Evy; Caixeta, Vanessa; Bloch, Katarzyna; Conradi, Lena-Christin; Treps, Lucas; Staes, An; Gevaert, Kris; Tee, Andrew; Dewerchin, Mieke; Semenkovich, Clay F.; Impens, Francis; Schilling, Birgit; Verdin, Eric; Swinnen, Johannes V.; Meier, Jordan L.; Kulkarni, Rhushikesh A.; Sickmann, Albert; Ghesquiere, Bart; Schoonjans, Luc; Li, Xuri; Mazzone, Massimiliano; Carmeliet, Peter published the artcile< Impairment of Angiogenesis by Fatty Acid Synthase Inhibition Involves mTOR Malonylation>, Quality Control of 1223001-51-1, the main research area is fatty acid synthase mTOR acetyl CoA malonylation angiogenesis; angiogenesis; endothelial cell; fatty acid synthase; lipids; mTOR; mTORC1; malonyl-CoA; metabolism; post-translational modifications; protein malonylation.
The role of fatty acid synthesis in endothelial cells (ECs) remains incompletely characterized. We report that fatty acid synthase knockdown (FASNKD) in ECs impedes vessel sprouting by reducing proliferation. Endothelial loss of FASN impaired angiogenesis in vivo, while FASN blockade reduced pathol. 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, FASNKDelevated 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 FASNKD 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.
Cell Metabolism published new progress about Angiogenesis. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Quality Control of 1223001-51-1.
Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem