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ResearchIn-Press PreviewCell biologyTherapeutics
Open Access | 10.1172/JCI178428
1College of Life and Health Sciences, Northeastern University, Shenyang, China
2Department of Pathology, The Fourth People’s Hospital of Shenyang, Shenyang, China
3Key Laboratory of Medical Cell Biology, China Medical University, Shenyang, China
4State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China
5Department of General Surgery, China Medical University, Shenyang, China
6College of Life and Health Sciences, Northeastern University, ShenYang, China
7State Key Laboratory of Electroanalytical Chemistry, Chinese Academy of Sciences, Changchun, China
Find articles by Zhang, H. in: JCI | PubMed | Google Scholar
1College of Life and Health Sciences, Northeastern University, Shenyang, China
2Department of Pathology, The Fourth People’s Hospital of Shenyang, Shenyang, China
3Key Laboratory of Medical Cell Biology, China Medical University, Shenyang, China
4State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China
5Department of General Surgery, China Medical University, Shenyang, China
6College of Life and Health Sciences, Northeastern University, ShenYang, China
7State Key Laboratory of Electroanalytical Chemistry, Chinese Academy of Sciences, Changchun, China
Find articles by Lin, J. in: JCI | PubMed | Google Scholar
1College of Life and Health Sciences, Northeastern University, Shenyang, China
2Department of Pathology, The Fourth People’s Hospital of Shenyang, Shenyang, China
3Key Laboratory of Medical Cell Biology, China Medical University, Shenyang, China
4State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China
5Department of General Surgery, China Medical University, Shenyang, China
6College of Life and Health Sciences, Northeastern University, ShenYang, China
7State Key Laboratory of Electroanalytical Chemistry, Chinese Academy of Sciences, Changchun, China
Find articles by Zheng, S. in: JCI | PubMed | Google Scholar
1College of Life and Health Sciences, Northeastern University, Shenyang, China
2Department of Pathology, The Fourth People’s Hospital of Shenyang, Shenyang, China
3Key Laboratory of Medical Cell Biology, China Medical University, Shenyang, China
4State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China
5Department of General Surgery, China Medical University, Shenyang, China
6College of Life and Health Sciences, Northeastern University, ShenYang, China
7State Key Laboratory of Electroanalytical Chemistry, Chinese Academy of Sciences, Changchun, China
Find articles by Ma, L. in: JCI | PubMed | Google Scholar
1College of Life and Health Sciences, Northeastern University, Shenyang, China
2Department of Pathology, The Fourth People’s Hospital of Shenyang, Shenyang, China
3Key Laboratory of Medical Cell Biology, China Medical University, Shenyang, China
4State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China
5Department of General Surgery, China Medical University, Shenyang, China
6College of Life and Health Sciences, Northeastern University, ShenYang, China
7State Key Laboratory of Electroanalytical Chemistry, Chinese Academy of Sciences, Changchun, China
Find articles by Pang, Z. in: JCI | PubMed | Google Scholar
1College of Life and Health Sciences, Northeastern University, Shenyang, China
2Department of Pathology, The Fourth People’s Hospital of Shenyang, Shenyang, China
3Key Laboratory of Medical Cell Biology, China Medical University, Shenyang, China
4State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China
5Department of General Surgery, China Medical University, Shenyang, China
6College of Life and Health Sciences, Northeastern University, ShenYang, China
7State Key Laboratory of Electroanalytical Chemistry, Chinese Academy of Sciences, Changchun, China
Find articles by Yin, H. in: JCI | PubMed | Google Scholar
1College of Life and Health Sciences, Northeastern University, Shenyang, China
2Department of Pathology, The Fourth People’s Hospital of Shenyang, Shenyang, China
3Key Laboratory of Medical Cell Biology, China Medical University, Shenyang, China
4State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China
5Department of General Surgery, China Medical University, Shenyang, China
6College of Life and Health Sciences, Northeastern University, ShenYang, China
7State Key Laboratory of Electroanalytical Chemistry, Chinese Academy of Sciences, Changchun, China
Find articles by Meng, C. in: JCI | PubMed | Google Scholar
1College of Life and Health Sciences, Northeastern University, Shenyang, China
2Department of Pathology, The Fourth People’s Hospital of Shenyang, Shenyang, China
3Key Laboratory of Medical Cell Biology, China Medical University, Shenyang, China
4State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China
5Department of General Surgery, China Medical University, Shenyang, China
6College of Life and Health Sciences, Northeastern University, ShenYang, China
7State Key Laboratory of Electroanalytical Chemistry, Chinese Academy of Sciences, Changchun, China
Find articles by Wang, Y. in: JCI | PubMed | Google Scholar
1College of Life and Health Sciences, Northeastern University, Shenyang, China
2Department of Pathology, The Fourth People’s Hospital of Shenyang, Shenyang, China
3Key Laboratory of Medical Cell Biology, China Medical University, Shenyang, China
4State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China
5Department of General Surgery, China Medical University, Shenyang, China
6College of Life and Health Sciences, Northeastern University, ShenYang, China
7State Key Laboratory of Electroanalytical Chemistry, Chinese Academy of Sciences, Changchun, China
Find articles by Han, Q. in: JCI | PubMed | Google Scholar
1College of Life and Health Sciences, Northeastern University, Shenyang, China
2Department of Pathology, The Fourth People’s Hospital of Shenyang, Shenyang, China
3Key Laboratory of Medical Cell Biology, China Medical University, Shenyang, China
4State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China
5Department of General Surgery, China Medical University, Shenyang, China
6College of Life and Health Sciences, Northeastern University, ShenYang, China
7State Key Laboratory of Electroanalytical Chemistry, Chinese Academy of Sciences, Changchun, China
Find articles by Zhang, X. in: JCI | PubMed | Google Scholar
1College of Life and Health Sciences, Northeastern University, Shenyang, China
2Department of Pathology, The Fourth People’s Hospital of Shenyang, Shenyang, China
3Key Laboratory of Medical Cell Biology, China Medical University, Shenyang, China
4State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China
5Department of General Surgery, China Medical University, Shenyang, China
6College of Life and Health Sciences, Northeastern University, ShenYang, China
7State Key Laboratory of Electroanalytical Chemistry, Chinese Academy of Sciences, Changchun, China
Find articles by Li, Z. in: JCI | PubMed | Google Scholar
1College of Life and Health Sciences, Northeastern University, Shenyang, China
2Department of Pathology, The Fourth People’s Hospital of Shenyang, Shenyang, China
3Key Laboratory of Medical Cell Biology, China Medical University, Shenyang, China
4State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China
5Department of General Surgery, China Medical University, Shenyang, China
6College of Life and Health Sciences, Northeastern University, ShenYang, China
7State Key Laboratory of Electroanalytical Chemistry, Chinese Academy of Sciences, Changchun, China
Find articles by Cao, L. in: JCI | PubMed | Google Scholar
1College of Life and Health Sciences, Northeastern University, Shenyang, China
2Department of Pathology, The Fourth People’s Hospital of Shenyang, Shenyang, China
3Key Laboratory of Medical Cell Biology, China Medical University, Shenyang, China
4State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China
5Department of General Surgery, China Medical University, Shenyang, China
6College of Life and Health Sciences, Northeastern University, ShenYang, China
7State Key Laboratory of Electroanalytical Chemistry, Chinese Academy of Sciences, Changchun, China
Find articles by Liu, L. in: JCI | PubMed | Google Scholar
1College of Life and Health Sciences, Northeastern University, Shenyang, China
2Department of Pathology, The Fourth People’s Hospital of Shenyang, Shenyang, China
3Key Laboratory of Medical Cell Biology, China Medical University, Shenyang, China
4State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China
5Department of General Surgery, China Medical University, Shenyang, China
6College of Life and Health Sciences, Northeastern University, ShenYang, China
7State Key Laboratory of Electroanalytical Chemistry, Chinese Academy of Sciences, Changchun, China
Find articles by Fei, T. in: JCI | PubMed | Google Scholar
1College of Life and Health Sciences, Northeastern University, Shenyang, China
2Department of Pathology, The Fourth People’s Hospital of Shenyang, Shenyang, China
3Key Laboratory of Medical Cell Biology, China Medical University, Shenyang, China
4State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China
5Department of General Surgery, China Medical University, Shenyang, China
6College of Life and Health Sciences, Northeastern University, ShenYang, China
7State Key Laboratory of Electroanalytical Chemistry, Chinese Academy of Sciences, Changchun, China
Find articles by Gao, D. in: JCI | PubMed | Google Scholar
1College of Life and Health Sciences, Northeastern University, Shenyang, China
2Department of Pathology, The Fourth People’s Hospital of Shenyang, Shenyang, China
3Key Laboratory of Medical Cell Biology, China Medical University, Shenyang, China
4State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China
5Department of General Surgery, China Medical University, Shenyang, China
6College of Life and Health Sciences, Northeastern University, ShenYang, China
7State Key Laboratory of Electroanalytical Chemistry, Chinese Academy of Sciences, Changchun, China
Find articles by Yang, L. in: JCI | PubMed | Google Scholar
1College of Life and Health Sciences, Northeastern University, Shenyang, China
2Department of Pathology, The Fourth People’s Hospital of Shenyang, Shenyang, China
3Key Laboratory of Medical Cell Biology, China Medical University, Shenyang, China
4State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China
5Department of General Surgery, China Medical University, Shenyang, China
6College of Life and Health Sciences, Northeastern University, ShenYang, China
7State Key Laboratory of Electroanalytical Chemistry, Chinese Academy of Sciences, Changchun, China
Find articles by Peng, X. in: JCI | PubMed | Google Scholar
1College of Life and Health Sciences, Northeastern University, Shenyang, China
2Department of Pathology, The Fourth People’s Hospital of Shenyang, Shenyang, China
3Key Laboratory of Medical Cell Biology, China Medical University, Shenyang, China
4State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China
5Department of General Surgery, China Medical University, Shenyang, China
6College of Life and Health Sciences, Northeastern University, ShenYang, China
7State Key Laboratory of Electroanalytical Chemistry, Chinese Academy of Sciences, Changchun, China
Find articles by Ding, C. in: JCI | PubMed | Google Scholar
1College of Life and Health Sciences, Northeastern University, Shenyang, China
2Department of Pathology, The Fourth People’s Hospital of Shenyang, Shenyang, China
3Key Laboratory of Medical Cell Biology, China Medical University, Shenyang, China
4State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China
5Department of General Surgery, China Medical University, Shenyang, China
6College of Life and Health Sciences, Northeastern University, ShenYang, China
7State Key Laboratory of Electroanalytical Chemistry, Chinese Academy of Sciences, Changchun, China
Find articles by Wang, S. in: JCI | PubMed | Google Scholar
1College of Life and Health Sciences, Northeastern University, Shenyang, China
2Department of Pathology, The Fourth People’s Hospital of Shenyang, Shenyang, China
3Key Laboratory of Medical Cell Biology, China Medical University, Shenyang, China
4State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China
5Department of General Surgery, China Medical University, Shenyang, China
6College of Life and Health Sciences, Northeastern University, ShenYang, China
7State Key Laboratory of Electroanalytical Chemistry, Chinese Academy of Sciences, Changchun, China
Find articles by
Sheng, R.
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Published July 4, 2024 - More info
Cell cycle regulation is largely abnormal in cancers. Molecular understanding and therapeutic targeting of the aberrant cell cycle are essentially meaningful. Here, we identified an under-appreciated Serine/Threonine kinase, CDKL3 (Cyclin-dependent kinase like 3), crucially drives the rapid cell cycle progression and cell growth in cancers. Mechanism-wise, CDKL3 localizes in the nucleus and associates with specific cyclin to directly phosphorylate Retinoblastoma (Rb) for quiescence exit. In parallel, CDKL3 prevents the ubiquitin-proteasomal degradation of CDK4 by direct phosphorylation on T172 to sustain G1 phase advancement. The crucial function of CDKL3 in cancers was demonstrated both in vitro and in vivo. We also designed, synthesized and characterized a first-in-class CDKL3-specific inhibitor, HZ1. HZ1 exhibits greater potency than CDK4/6 (Cyclin-dependent kinase 4/6) inhibitor in pan-cancer treatment by causing cell cycle arrest and overcomes the acquired resistance of the latter. In particular, CDKL3 has significant clinical relevance in colon cancer, and the effectiveness of HZ1 was demonstrated by murine and patient-derived cancer models. Collectively, this work presented an integrated paradigm of cancer cell cycle regulation and suggested CDKL3-targeting as a feasible approach in cancer treatment.