Fig. 9: K235 acetylation of ALKBH5 is upregulated in cancers and is critical for the oncogenic roles of ALKBH5.

a–d The ALKBH5 protein level (a); cell proliferation (b) (n = 3); and migration, invasion (c) (n = 5), and colony formation (d) (n = 3) were determined in ALKBH5 KO HeLa cells stably re-expressing wild-type ALKBH5 or its mutants K235R or K235Q. e The in vivo tumorigenesis of the indicated ALKBH5 KO HeLa cells stably re-expressing wild-type ALKBH5 or its mutant K235R was examined, and the weights of the xenograft tumors were analyzed (n = 10 mice per group). f The levels of the indicated proteins were determined in ALKBH5 KO HeLa cells stably reexpressing wild-type ALKBH5 or its mutant K235R. g K235 acetylation and ALKBH5, KAT8, and HDAC7 levels were determined in ten pairs of fresh liver and gastric cancer tissues and their corresponding nontumor tissues. h A regulatory model of ALKBH5 m⁶A demethylation activity is elucidated in which K235-acetylated ALKBH5 primarily functions as the catalytic core, and PSPC1 serves as an RNA-binding platform to recruit and facilitate the recognition of RNA m⁶A by ALKBH5 by interacting with K235-acetylated ALKBH5, thereby promoting RNA m⁶A erasure. Two-tailed unpaired Student’s t test in c–e and two-way ANOVA in (b). The data are represented as the mean ± SD. **p < 0.01, ***p < 0.001, ns indicates no significance. Source data are provided as a Source Data file.