Description
ASH2L is the human homolog of the
Drosophila absent, small or homeotic discs 2 (ash2) gene product, a member of the trithorax group (TrxG) of proteins. The TrxG gene products in
Drosophila and their mammalian homologs are responsible for controlling gene transcription. The ASH2L protein is a component of various multisubunit protein complexes, including the large complex of proteins associated with the SET1 (MLL) family of lysine methyltransferases. ASH2L, along with WDR5 and RbBP5, form the human MLL1 core protein complex. MLL1-
5 protein complexes catalyze the di-
and trimethylation of histone H3 at lysine 4 (H3K4me2/me3), leading to the maintenance of global H3K4 trimethylation. Post-
translational modifications of ASH2L have also been described showing methylation of Arg-
296 by protein-
arginine methyltransferease 1 (PRMT1)
in vitro and in cells and by PRMT5
in vitro. Further experimental evidence in rats suggests that ASH2L cooperates with Ha-
RAS to transform rat embryonic fibroblasts, implicating ASH2L as a novel oncoprotein.
References
[1] JUN-HUA WANG. ASH2L: alternative splicing and downregulation during induced megakaryocytic differentiation of multipotential leukemia cell lines[J]. Journal of Molecular Medicine-Jmm, 2001, 27 1: 399-405. DOI:
10.1007/s001090100222[2] MELISSA M STEWARD. Molecular regulation of H3K4 trimethylation by ASH2L, a shared subunit of MLL complexes[J]. Nature Structural & Molecular Biology, 2006, 13 9: 852-854. DOI:
10.1038/nsmb1131[3] SAEID MOHAMMADPARAST Chenbei C. Ash2l, an obligatory component of H3K4 methylation complexes, regulates neural crest development[J]. Developmental biology, 2022, 492: Pages 14-24. DOI:
10.1016/j.ydbio.2022.09.008[4] YONG CHEN. Structure of the SPRY domain of human Ash2L and its interactions with RbBP5 and DPY30[J]. Cell Research, 2012, 22 3: 598-602. DOI:
10.1038/cr.2012.9[5] J. S. BUTLER. Low expression of ASH2L protein correlates with a favorable outcome in acute myeloid leukemia[J]. Leukemia & Lymphoma, 2017, 30 1: 1207-1218. DOI:
10.1080/10428194.2016.1235272
