iProXProteomicsGuangrong YanHomo Sapienshttp://www.iprox.org/page/project.html?id=IPX0002293000jxygr007@yahoo.comBiomedicine Research Center, The Third Affiliated Hospital of Guangzhou Medical UniversityiProXN6-methyladenosine (m⁶A) modification plays important roles in bioprocesses and diseases. AlkB homolog 5 (ALKBH5) is one of two m⁶A demethylases. Here, we reveal that ALKBH5 is acetylated at lysine 235 (K235) by lysine acetyltransferase 8 and deacetylated by histone deacetylase 7. K235 acetylation strengthens the m⁶A demethylation activity of ALKBH5 by increasing its recognition of m⁶A on mRNA. RNA-binding protein paraspeckle component 1 (PSCP1) is a regulatory subunit of ALKBH5 and preferentially interacts with K235-acetylated ALKBH5 to recruit and facilitate the recognition of m⁶A mRNA by ALKBH5, thereby promoting m⁶A erasure. Mitogenic signals promote ALKBH5 K235 acetylation. K235 acetylation of ALKBH5 is upregulated in cancers and promotes tumorigenesis. Thus, our findings reveal that the m⁶A demethylation activity of ALKBH5 is orchestrated by its K235 acetylation and regulatory subunit PSPC1 and that K235 acetylation is necessary for the m⁶A demethylase activity and oncogenic roles of ALKBH5.K235 acetylation couples with PSPC1 to regulate the m⁶A demethylation activity of ALKBH5 and tumorigenesis.Zhang Xiao-Lan XL, Chen Xin-Hui XH, Xu Binwu B, Chen Min M, Zhu Song S, Meng Nan N, Wang Ji-Zhong JZ, Zhu Huifang H, Chen De, Liu Jin-Bao JB, Yan Guang-Rong GRfalseIdentification the interactors of the K235-acetylated ALKBH5The differntial gel band between wild-type ALKBH5-interacted proteins and K235R mutant ALKBH5-interacted proteins was identifed by mass spectrometry.Thu Apr 13 00:00:00 BST 2023PXD020071960637369679