Cdc2-like kinases: structure, biological function, and therapeutic targets for diseases

Mengqiu Song; Luping Pang; Mengmeng Zhang; Yingzi Qu; Kyle Vaughn Laster; Zigang Dong

doi:10.1038/s41392-023-01409-4

Cdc2-like kinases: structure, biological function, and therapeutic targets for diseases

Signal Transduct Target Ther. 2023 Apr 7;8(1):148. doi: 10.1038/s41392-023-01409-4.

Authors

Mengqiu Song^{1

2

3}, Luping Pang^{3

4

5}, Mengmeng Zhang^{1

4}, Yingzi Qu^{1

4}, Kyle Vaughn Laster², Zigang Dong^{6

7

8

9}

Affiliations

¹ Department of Pathophysiology, School of Basic Medical Sciences, College of Medicine, Zhengzhou University, Zhengzhou, Henan, 450001, China.
² China-US (Henan) Hormel Cancer Institute, No.127, Dongming Road, Jinshui District, Zhengzhou, Henan, 450008, China.
³ State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, Henan, China.
⁴ Academy of Medical Sciences, College of Medicine, Zhengzhou University, Zhengzhou, Henan, 450001, China.
⁵ Research Center of Basic Medicine, Academy of Medical Sciences, College of Medicine, Zhengzhou University, Zhengzhou, Henan, 450001, China.
⁶ Department of Pathophysiology, School of Basic Medical Sciences, College of Medicine, Zhengzhou University, Zhengzhou, Henan, 450001, China. dongzg@zzu.edu.cn.
⁷ China-US (Henan) Hormel Cancer Institute, No.127, Dongming Road, Jinshui District, Zhengzhou, Henan, 450008, China. dongzg@zzu.edu.cn.
⁸ State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, Henan, China. dongzg@zzu.edu.cn.
⁹ Academy of Medical Sciences, College of Medicine, Zhengzhou University, Zhengzhou, Henan, 450001, China. dongzg@zzu.edu.cn.

Abstract

The CLKs (Cdc2-like kinases) belong to the dual-specificity protein kinase family and play crucial roles in regulating transcript splicing via the phosphorylation of SR proteins (SRSF1-12), catalyzing spliceosome molecular machinery, and modulating the activities or expression of non-splicing proteins. The dysregulation of these processes is linked with various diseases, including neurodegenerative diseases, Duchenne muscular dystrophy, inflammatory diseases, viral replication, and cancer. Thus, CLKs have been considered as potential therapeutic targets, and significant efforts have been exerted to discover potent CLKs inhibitors. In particular, clinical trials aiming to assess the activities of the small molecules Lorecivivint on knee Osteoarthritis patients, and Cirtuvivint and Silmitasertib in different advanced tumors have been investigated for therapeutic usage. In this review, we comprehensively documented the structure and biological functions of CLKs in various human diseases and summarized the significance of related inhibitors in therapeutics. Our discussion highlights the most recent CLKs research, paving the way for the clinical treatment of various human diseases.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Humans
Phosphorylation
Protein Processing, Post-Translational
Protein Serine-Threonine Kinases* / genetics
Protein-Tyrosine Kinases* / genetics
RNA Splicing
Serine-Arginine Splicing Factors

Substances

Protein Serine-Threonine Kinases
Protein-Tyrosine Kinases
SRSF1 protein, human
Serine-Arginine Splicing Factors