biostudies-literatureLai YNHLBI NIH HHSNational Institutes of Health3578-3587https://www.ebi.ac.uk/biostudies/studies/S-EPMC5665448biostudies-literatureUnknown130(20)E3 ubiquitin ligase recognizes its protein substrates via specific molecular signatures for ubiquitin proteasomal degradation. However, the role of acetylation/deacetylation in the process of E3 ubiquitin ligase recognizing its protein substrates is not fully studied. Here, we report that a tandem IK motif in protein arginine methyltransferase 1 (PRMT1) forms an acetyldegron to recruit the F-box/LRR-repeat protein 17 (FBXL17), a component of the SKP1-CUL1-F-box protein (SCF)-type E3 ubiquitin ligase complex. PRMT1 is polyubiquitylated for proteasome degradation with a half-life of approximately 4 h in lung epithelial cells. SCF^Fbxl17 mediates PRMT1 polyubiquitylation at K117. SCF^Fbxl17 specifically binds PRMT1 via a unique motif IKxxxIK. Strikingly, the acetylation/deJournal of cell scienceLipopolysaccharide modulates p300 and Sirt1 to promote PRMT1 stability via an SCF^Fbxl17-recognized acetyldegron.PMC5665448R01 grant HL125435R01 HL125435Lai YLi XLi JZou CfalseLipopolysaccharide modulates p300 and Sirt1 to promote PRMT1 stability via an SCF^Fbxl17-recognized acetyldegron.E3 ubiquitin ligase recognizes its protein substrates via specific molecular signatures for ubiquitin proteasomal degradation. However, the role of acetylation/deacetylation in the process of E3 ubiquitin ligase recognizing its protein substrates is not fully studied. Here, we report that a tandem IK motif in protein arginine methyltransferase 1 (PRMT1) forms an acetyldegron to recruit the F-box/LRR-repeat protein 17 (FBXL17), a component of the SKP1-CUL1-F-box protein (SCF)-type E3 ubiquitin ligase complex. PRMT1 is polyubiquitylated for proteasome degradation with a half-life of approximately 4 h in lung epithelial cells. SCF^Fbxl17 mediates PRMT1 polyubiquitylation at K117. SCF^Fbxl17 specifically binds PRMT1 via a unique motif IKxxxIK. Strikingly, the acetylation/de2017-01-01T00:00:00Z2017 Oct2025-06-01T03:54:17.183Z2025-06-01T03:54:17.183ZS-EPMC56654482888309510.1242/jcs.206904