异位Hsp70调节剂YM-1诱导BRD4降解

IF 1.5 4区医学 Q4 CHEMISTRY, MEDICINAL Chemical & pharmaceutical bulletin Pub Date : 2024-02-01 DOI:10.1248/cpb.c23-00543

Yugo Mishima, Shusuke Tomoshige, Shinichi Sato, Minoru Ishikawa

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引用次数: 0

摘要

YM-1 是热休克 70 kDa 蛋白（Hsp70）的一种异位调节剂，可抑制癌细胞生长，但其机制尚未完全清楚。在这里，我们发现 YM-1 能诱导含溴结构域 4（BRD4）的降解，而 BRD4 能介导癌基因的表达。总体而言，我们的研究结果表明，YM-1 促进 HSP70 与 BRD4 结合，进而促进与 Hsp70 协同工作的 E3 泛素连接酶 Hsc70-interacting protein (CHIP) 的 C 端泛素化 BRD4，导致 BRD4 蛋白质体降解。YM-1 诱导的 BRD4 减少至少部分有助于抑制癌细胞的生长。

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Allosteric Hsp70 Modulator YM-1 Induces Degradation of BRD4

YM-1, an allosteric modulator of heat-shock 70 kDa protein (Hsp70), inhibits cancer cell growth, but the mechanism is not yet fully understood. Here, we show that YM-1 induces the degradation of bromodomain containing 4 (BRD4), which mediates oncogene expression. Overall, our results indicate that YM-1 promotes the binding of HSP70 to BRD4, and this in turn promotes the ubiquitination of BRD4 by C-terminus of Hsc70-interacting protein (CHIP), an E3 ubiquitin ligase working in concert with Hsp70, leading to proteasomal degradation of BRD4. This YM-1-induced decrease of BRD4 would contribute at least in part to the inhibition of cancer cell growth.

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来源期刊

Chemical & pharmaceutical bulletin 医学-化学综合

CiteScore

3.20

自引率

5.90%

发文量

132

审稿时长

1.7 months

期刊介绍： The CPB covers various chemical topics in the pharmaceutical and health sciences fields dealing with biologically active compounds, natural products, and medicines, while BPB deals with a wide range of biological topics in the pharmaceutical and health sciences fields including scientific research from basic to clinical studies. For details of their respective scopes, please refer to the submission topic categories below. Topics: Organic chemistry In silico science Inorganic chemistry Pharmacognosy Health statistics Forensic science Biochemistry Pharmacology Pharmaceutical care and science Medicinal chemistry Analytical chemistry Physical pharmacy Natural product chemistry Toxicology Environmental science Molecular and cellular biology Biopharmacy and pharmacokinetics Pharmaceutical education Chemical biology Physical chemistry Pharmaceutical engineering Epidemiology Hygiene Regulatory science Immunology and microbiology Clinical pharmacy Miscellaneous.