Kynurenine derivative 3-HAA is an agonist ligand for transcription factor YY1

Abstract

Abstract The 3-hydroxyanthranilic acid (3-HAA), a derivative of kynurenine, was reported to suppress tumor growth. However, the function of 3-HAA largely remains unclear. Here, we report that 3-hydroxyanthranilic acid (3-HAA) is lower in tumor cells, while adding exogenous 3-HAA induces apoptosis in hepatocellular carcinoma by binding YY1. This 3-HAA binding of YY1 leads to phosphorylation of YY1 at the Thr 398 by PKCζ, concomitantly enhances YY1 chromatin binding activity to increase expression of target genes. These findings demonstrate that 3-HAA is a ligand of YY1, suggesting it is a promising therapeutic candidate for HCC.

Keywords

• 3-Hydroxyanthronic acid (3-HAA)
• Kynurenine
• YY1
• DUSP6
• Hepatocellular carcinoma (HCC)
• Tryptophan metabolism