Histone Deacetylase Inhibitors (HDACi) Promote KLF5 Ubiquitination and Degradation in Basal-like Breast Cancer

Autor: Yanjie Kong, Wenlong Ren, Huan Fang, Naseer Ali Shah, Yujie Shi, Dingyun You, Chengang Zhou, Dewei Jiang, Chuanyu Yang, Huichun Liang, Wenjin Liu, Luzhen Wang, Wenqiang Gan, Xing Wan, Fubing Li, Zhen Li, Ceshi Chen, Ni Xie
Rok vydání: 2021
Předmět:
Zdroj: International journal of biological sciences. 18(5)
ISSN: 1449-2288
Popis: Basal-like breast cancer (BLBC) accounts for approximately 15% of all breast cancer cases, and patients with BLBC have a low survival rate. Our previous study demonstrated that the KLF5 transcription factor promotes BLBC cell proliferation and tumor growth. In this study, we demonstrated that the histone deacetylase inhibitors (HDACi), suberoylanilide hydroxamic acid (SAHA), and trichostatin A (TSA), increased KLF5 acetylation at lysine 369 (K369), downregulated KLF5 protein expression levels, and decreased cell viability in BLBC cell lines. HDACi target KLF5 for proteasomal degradation by promoting KLF5 protein ubiquitination. K369 acetylation of KLF5 decreases the binding between KLF5 and its deubiquitinase, BAP1. These findings revealed a novel mechanism by which HDACi suppress BLBC, and a novel crosstalk between KLF5 protein acetylation and ubiquitination.
Databáze: OpenAIRE