Targeting Cul3-scaffold E3 ligase complex via KLHL substrate adaptors for cancer therapy

被引：17

作者：

Xiang, Senfeng ^{[1
]}

Shi, Xiaoxian ^{[1
]}

Chen, Pengfei ^{[1
]}

Chen, Yifan ^{[1
]}

Bing, Shaowei ^{[1
]}

Jin, Xizhi ^{[1
]}

Cao, Ji ^{[1
,3
]}

Wang, Jinhu ^{[2
,3
]}

Yang, Bo ^{[1
,3
]}

Shao, Xuejing ^{[1
]}

He, Qiaojun ^{[1
,3
,4
,5
]}

Ying, Meidan ^{[1
,2
,3
]}

机构：

[1] Zhejiang Univ, Coll Pharmaceut Sci, Inst Pharmacol & Toxicol, Zhejiang Prov Key Lab Anticanc Drug Res, Hangzhou 310058, Peoples R China

[2] Zhejiang Univ, Childrens Hosp, Natl Clin Res Ctr Child Hlth, Sch Med, Hangzhou 310052, Peoples R China

[3] Zhejiang Univ, Canc Ctr, Hangzhou 310058, Peoples R China

[4] Zhejiang Univ, Innovat Inst Artificial Intelligence Med, Hangzhou 310058, Peoples R China

[5] Zhejiang Univ, Affiliated Hosp 2, Dept Surg, Sch Med, Hangzhou 310009, Peoples R China

来源：

PHARMACOLOGICAL RESEARCH | 2021年 / 169卷

基金：

中国国家自然科学基金;

关键词：

KLHL; Cullin3-RING Ligase; Substrate adaptor; Target discovery; Cancer therapy; NEDD8-ACTIVATING ENZYME; UBIQUITIN LIGASES; IDENTIFICATION; INHIBITOR; DISEASE; FAMILY;

D O I：

10.1016/j.phrs.2021.105616

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

Targeted therapy has become increasingly important and indispensable in cancer therapy. Cullin3-RING ligases (CRL3) serve as essential executors for regulating protein homeostasis in cancer development, highlighting that CRL3 might be promising targets in various cancer treatment. However, how to design new targeted therapies by disrupting the function of CRL3 is poorly understood. Here, we focus on the substrate adaptors of CRL3, and carry out a systematical research on the function of Kelch-like (KLHL) family proteins. We have identified twenty-four KLHL proteins with function of tumor promotion and thirteen KLHL proteins with high clinical significance on cancer therapy. Furthermore, we have clarified the novel biological function of KLHL13 as a vital factor that contributes to malignant progression in lung cancer. Taken together, our findings reveal multiple potential therapeutical targets and provide evidence for targeting CRL3 via KLHL substrate adaptors for cancer therapy.

引用

页数：13

共 32 条

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