Discovery of a fluorescigenic pyrazoline derivative targeting ubiquitin

被引：4

作者：

Chen, XinPeng ^{[1
,2
]}

Lin, ZhaoMin ^{[3
]}

Su, Le ^{[1
]}

Cui, XiaoLing ^{[1
]}

Zhao, BaoXiang ^{[4
]}

Miao, JunYing ^{[1
,5
,6
]}

机构：

[1] Shandong Univ, Sch Life Sci, Shandong Prov Key Lab Anim Cells & Dev Biol, Jinan 250100, Peoples R China

[2] Hubei Normal Univ, Sch Life Sci, Hubei Key Lab Edible Wild Plants Conservat & Util, Huangshi 435002, Hubei, Peoples R China

[3] Shandong Univ, Inst Med Sci, Hosp 2, Jinan 250033, Peoples R China

[4] Shandong Univ, Sch Chem & Chem Engn, Inst Organ Chem, Jinan 250100, Peoples R China

[5] Shandong Univ, Key Lab Cardiovasc Remodeling & Funct Res, Chinese Minist Educ, Qilu Hosp, Jinan 250012, Peoples R China

[6] Shandong Univ, Chinese Minist Hlth, Qilu Hosp, Jinan 250012, Peoples R China

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2020年 / 528卷 / 02期

基金：

中国国家自然科学基金;

关键词：

Fluorescigenic pyrazoline derivatives; Ubiquitin; BECN1; Autophagy; CANCER-CELLS; AUTOPHAGY; PROTEINS; MACHINERY; ENZYMES;

D O I：

10.1016/j.bbrc.2020.05.142

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Despite significant process in ubiquitin modification by using traditional genetic methods, chemical small molecules that directly target and modify ubiquitin are little reported. Here, we find that a fluorescigenic pyrazoline derivative (FPD5) could do so effectively. Molecule docking revealed that lysine 11 of ubiquitin was the key contact residue. FPD5, with stronger fluorescence, elevated the ubiquitination of beclin 1 (BECN1) and promoted autophagy. This study highlights that targeting ubiquitin by chemical small molecules enables us to modulate ubiquitination and the downstream signaling in the ubiquitin system. (C) 2020 Elsevier Inc. All rights reserved.

引用

页码：256 / 260

页数：5

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