Competition for cysteine acylation by C16:0 and C18:0 derived lipids is a global phenomenon in the proteome.

Autor:	Nůsková H; Division of Signal Transduction in Cancer and Metabolism, German Cancer Research Center (DKFZ), Heidelberg, Germany., Cortizo FG; Division of Signal Transduction in Cancer and Metabolism, German Cancer Research Center (DKFZ), Heidelberg, Germany., Schwenker LS; Division of Signal Transduction in Cancer and Metabolism, German Cancer Research Center (DKFZ), Heidelberg, Germany., Sachsenheimer T; Heidelberg University Biochemistry Center (BZH), Heidelberg, Germany., Diakonov EE; Division of Signal Transduction in Cancer and Metabolism, German Cancer Research Center (DKFZ), Heidelberg, Germany., Tiebe M; Division of Signal Transduction in Cancer and Metabolism, German Cancer Research Center (DKFZ), Heidelberg, Germany., Schneider M; Mass Spectrometry Based Protein Analysis Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany., Lohbeck J; Research Group Cancer Drug Development, German Cancer Research Center (DKFZ), Heidelberg, Germany., Reid C; Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany., Kopp-Schneider A; Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany., Helm D; Mass Spectrometry Based Protein Analysis Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany., Brügger B; Heidelberg University Biochemistry Center (BZH), Heidelberg, Germany., Miller AK; Research Group Cancer Drug Development, German Cancer Research Center (DKFZ), Heidelberg, Germany., Teleman AA; Division of Signal Transduction in Cancer and Metabolism, German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: a.teleman@dkfz.de.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2023 Sep; Vol. 299 (9), pp. 105088. Date of Electronic Publication: 2023 Jul 24.
DOI:	10.1016/j.jbc.2023.105088
Abstrakt:	S-acylation is a reversible posttranslational protein modification consisting of attachment of a fatty acid to a cysteine via a thioester bond. Research over the last few years has shown that a variety of different fatty acids, such as palmitic acid (C16:0), stearate (C18:0), or oleate (C18:1), are used in cells to S-acylate proteins. We recently showed that GNAI proteins can be acylated on a single residue, Cys3, with either C16:0 or C18:1, and that the relative proportion of acylation with these fatty acids depends on the level of the respective fatty acid in the cell's environment. This has functional consequences for GNAI proteins, with the identity of the acylating fatty acid affecting the subcellular localization of GNAIs. Unclear is whether this competitive acylation is specific to GNAI proteins or a more general phenomenon in the proteome. We perform here a proteome screen to identify proteins acylated with different fatty acids. We identify 218 proteins acylated with C16:0 and 308 proteins acylated with C18-lipids, thereby uncovering novel targets of acylation. We find that most proteins that can be acylated by C16:0 can also be acylated with C18-fatty acids. For proteins with more than one acylation site, we find that this competitive acylation occurs on each individual cysteine residue. This raises the possibility that the function of many different proteins can be regulated by the lipid environment via differential S-acylation. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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