Validation of selective catalytic BmCBP inhibitors that regulate the Bm30K-24 protein expression in silkworm, Bombyx mori.

IF 2.3 2区 农林科学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Jiasheng Geng, Weina Lu, Qinglong Kong, Jiao Lv, Yue Liu, Guowei Zu, Yanmei Chen, Caiying Jiang, Zhengying You, Zuoming Nie
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引用次数: 0

Abstract

The cAMP response element binding protein (CREB)-binding protein (CBP) is a histone acetyltransferase that plays an indispensable role in regulating the acetylation of histone and non-histone proteins. Recently, it has been discovered that chemical inhibitors A485 and C646 can bind to Bombyx mori's CBP (BmCBP) and inhibit its acetyltransferase activity. Notably, the binding ability of A485 with BmCBP showed a very low Kd value of 48 nM by surface plasmon resonance (SPR) test. Further identification showed that both A485 and C646 can decrease the acetylation level of known substrate H3K27 and only 1 μM of A485 can almost completely inhibit the acetylation of H3K27, suggesting that A485 is an effective inhibitor of BmCBP's acetyltransferase activity. Moreover, it was confirmed that A485 could downregulate the expression of acetylated Bm30K-24 protein at a post-translational level through acetylation modification by BmCBP. Additionally, it was found that A485 can downregulate the stability of Bm30K-24 and improve its ubiquitination level, suggesting that the acetylation modification by BmCBP could compete with ubiquitination modification at the same lysine site on Bm30K-24, thereby affecting its protein stability. Here, we predict that A485 may be a potent CBP acetyltransferase inhibitor which could be utilized to inhibit acetyltransferase activity in insects, including silkworms.

验证调节家蚕 Bm30K-24 蛋白表达的选择性催化 BmCBP 抑制剂
cAMP 反应元件结合蛋白(CREB)结合蛋白(CBP)是一种组蛋白乙酰转移酶,在调节组蛋白和非组蛋白的乙酰化过程中发挥着不可或缺的作用。最近研究发现,化学抑制剂 A485 和 C646 能与蚕宝宝的 CBP(BmCBP)结合并抑制其乙酰转移酶活性。值得注意的是,通过表面等离子体共振(SPR)测试,A485 与 BmCBP 的结合能力显示出 48 nM 的极低 Kd 值。进一步鉴定表明,A485和C646都能降低已知底物H3K27的乙酰化水平,只有1 μM的A485才能几乎完全抑制H3K27的乙酰化,这表明A485是BmCBP乙酰转移酶活性的有效抑制剂。此外,研究还证实 A485 可通过 BmCBP 的乙酰化修饰,在翻译后水平上下调乙酰化 Bm30K-24 蛋白的表达。此外,研究还发现 A485 可以降低 Bm30K-24 的稳定性,提高其泛素化水平,这表明 BmCBP 的乙酰化修饰可能会与 Bm30K-24 上相同赖氨酸位点的泛素化修饰发生竞争,从而影响其蛋白质的稳定性。在此,我们预测 A485 可能是一种强效的 CBP 乙酰转移酶抑制剂,可用于抑制包括家蚕在内的昆虫的乙酰转移酶活性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Insect Molecular Biology
Insect Molecular Biology 生物-昆虫学
CiteScore
4.80
自引率
3.80%
发文量
68
审稿时长
6-12 weeks
期刊介绍: Insect Molecular Biology has been dedicated to providing researchers with the opportunity to publish high quality original research on topics broadly related to insect molecular biology since 1992. IMB is particularly interested in publishing research in insect genomics/genes and proteomics/proteins. This includes research related to: • insect gene structure • control of gene expression • localisation and function/activity of proteins • interactions of proteins and ligands/substrates • effect of mutations on gene/protein function • evolution of insect genes/genomes, especially where principles relevant to insects in general are established • molecular population genetics where data are used to identify genes (or regions of genomes) involved in specific adaptations • gene mapping using molecular tools • molecular interactions of insects with microorganisms including Wolbachia, symbionts and viruses or other pathogens transmitted by insects Papers can include large data sets e.g.from micro-array or proteomic experiments or analyses of genome sequences done in silico (subject to the data being placed in the context of hypothesis testing).
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