Fig. 4: SUMO2-K11la hinders the sumoylation of ACSL4 at K500 site to promote ACSL4 degradation. | Cell Discovery

Fig. 4: SUMO2-K11la hinders the sumoylation of ACSL4 at K500 site to promote ACSL4 degradation.

From: Ferroptosis-induced SUMO2 lactylation counteracts ferroptosis by enhancing ACSL4 degradation in lung adenocarcinoma

Fig. 4

a Quantitative SUMOylome profiling in LUAD cells under RSL3-induced ferroptosis (2 μM, 24 h) identified ACSL4-K500 as a dynamically regulated sumoylation site. b The B-y ion matching diagram of ACSL4-K500 sumoylated site. c Proximity ligation assay (PLA) confirmed enhanced SUMO2-ACSL4 interaction in SUMO2-K11R mutants. PLA: red; DAPI: blue. Scale bars, 10 μm. d Co-IP assays demonstrated suppression of SUMO2/3-mediated ACSL4 sumoylation by NALA or FINs, and its augmentation by sodium oxamate. e SUMO2-K11R mutation abolished lactylation-dependent regulation and hyper-sumoylated ACSL4. f Lipidomics revealed elevated PE-arachidonic acid (PE-AdA, 20:4) and PE-adrenic acid (PE-AA, 22:4) in SUMO2-K11R cells. g CHX chase assays showed accelerated ACSL4 degradation upon NALA/FIN treatment, reversed by sodium oxamate or SUMO2-K11R in A549 cells. h Proteasomal inhibitor MG132 (10 μM), but not lysosomal inhibitor chloroquine (20 μM), rescued ACSL4 degradation in A549 cells. i Ubiquitination assays indicated increased polyubiquitination of ACSL4 following NALA/FIN treatment or SUMO2 knockdown, contrasting with sodium oxamate-mediated suppression in A549 cells.

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