2021
DOI: 10.1101/2021.07.27.454011
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Targeted Protein Acetylation in Cells Using Heterobifunctional Molecules

Abstract: Protein acetylation is a central event in orchestrating diverse cellular processes. However, current strategies to investigate protein acetylation in cells are often non-specific or lack temporal and magnitude control. Here, we developed an acetylation tagging system, AceTAG, to induce acetylation of targeted proteins. The AceTAG system utilizes bifunctional molecules to direct the lysine acetyltransferase p300/CBP to proteins fused with the small protein tag FKBP12F36V, resulting in their induced acetylation.… Show more

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Cited by 7 publications
(9 citation statements)
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“…18B), acetylation-tagging system (AceTAG) to recruit acetylation (Fig. 18C), 138 and nanobody-engineered O-GlcNAc transferase (OGT) 139 or split O-GlcNAcase (OGA) 140 for targeted protein glycosylation and deglycosylation (Fig. 18D).…”
Section: Discussionmentioning
confidence: 99%
“…18B), acetylation-tagging system (AceTAG) to recruit acetylation (Fig. 18C), 138 and nanobody-engineered O-GlcNAc transferase (OGT) 139 or split O-GlcNAcase (OGA) 140 for targeted protein glycosylation and deglycosylation (Fig. 18D).…”
Section: Discussionmentioning
confidence: 99%
“…19,26,27,49 producing these heterobifunctional molecules are nanobody-O,N-acetylglucosamine (GlcNAc) transferase (OGT) and AceTAG (Figure 2 and Table 1). 28,50,51 In addition to protein-targeted molecules, RNA-targeted therapies have attracted attention in recent years. Major technologies include oligonucleotide-based approaches such as RNA interference, antisense oligonucleotide (ASO)-based modalities, small molecules that recognize RNA structure, sequence-based molecules, and clustered regularly interspaced short palindromic repeats (CRISPR)-based strategies.…”
Section: Rational Strategies Of Heterobifunctional Molecule Designmentioning
confidence: 99%
“…To realize acetylation regulation, Wang et al proposed an acetylation tagging system, AceTAG, to induce the acetylation of targeted proteins via heterobifunctional molecules. 28 The first AceTAG utilized a KAT inhibitor linked with an FKBP12 F36V -binding ligand (Figure 8B). These heterobifunctional molecules modulated the distance between endogenous KATs and the FKBP12 F36V -tagged POIs, thus inducing the substrate-proximity-based acetylation (Figure 8C).…”
Section: Heterobifunctional Molecules Designed By Recruiting Endogeno...mentioning
confidence: 99%
“…13-15 Mirroring the use of CIPs with genetic fusion proteins, additional emerging applications include targeting proteins to kinases 16 or phosphatases, 17,18 recruiting deubiquitinases to a target protein for stabilization, 19 and recruiting histone acetyltransferases for targeted protein acetylation. 20…”
Section: Introductionmentioning
confidence: 99%