PHD finger protein 23 (PHF23)

PHD finger protein 23 (PHF23) is a nuclear, chromatin-associated protein characterized by a PHD (plant homeodomain) finger domain, which acts as a specialized "reader" of methylation marks, particularly recognizing trimethylated lysine 4 on histone H3 (H3K4me3). PHF23 regulates gene expression by binding to chromatin and recruiting other transcriptional machinery. It plays key roles in negative regulation of autophagy via modulation of ubiquitination pathways and in regulating chromatin structure and gene activation or repression. A chromosomal fusion between NUP98 and PHF23 produces a potent oncogenic driver of acute myeloid leukemia (AML), with the fusion protein hijacking the chromatin-binding specificity of PHF23 to aberrantly activate leukemogenic gene expression programs. The PHD finger domain of PHF23 and its fusion proteins has become a therapeutic target, with compounds like disulfiram showing preclinical efficacy in blocking PHF23-H3K4me3 interactions and inducing cancer cell death. Germline mutations in PHF23 are implicated in rare hereditary neuropathies and myasthenic syndromes.

Other names

FLJ16355MGC2941PDH-containing protein JUNE-1hJUNE-1bPHF23aPHD-containing protein JUNE-1PHD finger protein 23a

Small molecules (e.g., disulfiram) inhibit PHF23 by blocking its binding to trimethylated H3K4 (H3K4me3), thereby disrupting leukemogenic gene activation in AML models with NUP98-PHF23 fusion