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

Journal of Hematology & Oncology

卷:14

Youqiong Ye¹  Xiang Xu¹  Yuan Yuan¹  Jun Mi¹  Guifang Gan¹  Jieying Zhang¹  Aiwu Zhou¹  Zhaopeng Shi¹  Naixia Zhang²  Bo Bi³  Jixi Li⁴  Shuhai Lin⁵  Wen Liu⁶  Xianfu Gao⁷  Wenbin Zeng⁸  Pengfei Xu⁸ 

[1] Basic Medical Institute, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine;

[2] CAS Key Laboratory of Receptor Research, Department of Analytical Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences;

[3] Department of Nuclear Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine;

[4] School of Life Science, Fudan University;

[5] School of Life Sciences, State Key Laboratory of Cellular Stress Biology, Xiamen University;

[6] School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Xiamen University;

[7] Shanghai Profleader Biotech Co., Ltd;

[8] Xiangya School of Pharmaceutical Sciences, Central South University;

关键词: 3-Hydroxyanthronic acid (3-HAA);    Kynurenine;    YY1;    DUSP6;    Hepatocellular carcinoma (HCC);    Tryptophan metabolism;   

DOI  :  10.1186/s13045-021-01165-4

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown