An overview of CDK3 in cancer: clinical significance and pharmacological implications. (June 2022)

• Record Type: Journal Article
• Authors: Teo, Theodosia; Kasirzadeh, Sara; Albrecht, Hugo; Sykes, Matthew J.; Yang, Yuchao; Wang, Shudong
• Is Part Of: Pharmacological research. Volume 180(2022)
• Publication Date: 2022-06
• Subjects: AT7519 (PubChem CID: 11338033) -- BAY1000394 (PubChem CID: 45380979) -- CYC065 (PubChem CID: 24983461) -- NU6102 (PubChem CID: 4566) -- Purvalanol A (PubChem CID: 456214) -- R547 (PubChem CID: 6918852) -- RO-3306 (PubChem CID: 135400873) -- SNX9–1 (PubChem ID: 739323) -- tamoxifen (PubChem CID: 2733526) -- TG02 (PubChem CID: 16739650); AP-1 Activator protein-1 -- ATF-1 Activating transcription factor-1 -- CAK CDK-activating kinase -- CDC2 Cell division control 2 -- CDK Cyclin-dependent kinase -- cyc Cyclin -- E2F E2 factor -- ERα Estrogen receptor α -- ICN1 Intracellular domain of Notch1 -- IK3-1 Interactor with CDK3 1 -- NFAT3 Nuclear factor of activated T cell 3 -- NPC Nasopharyngeal carcinoma -- Rb Retinoblastoma -- SP Serine-proline rich -- TAM Tamoxifen; Cyclin-dependent kinase -- Cancer -- Targeted cancer therapy -- Cell cycle -- Transcription -- Pharmacology; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2022.106249
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: Cyclin-dependent kinase 3 (CDK3) is a major player driving retinoblastoma (Rb) phosphorylation during the G0 /G1 transition and in the early G1 phase of the cell cycle, preceding the effects of CDK4/cyclin D, CDK6/cyclin D, and CDK2/cyclin E. CDK3 can also directly regulate the activity of E2 factor (E2F) by skipping the role of Rb in late G1, potentially via the phosphorylation of the E2F1 partner DP1. Beyond the cell cycle, CDK3 interacts with various transcription factors involved in cell proliferation, differentiation, and transformation driven by the epidermal growth factor receptor (EGFR)/rat sarcoma virus (Ras) signaling pathway. The expression of CDK3 is extremely low in normal human tissue but upregulated in many cancers, implying a profound role in oncogenesis. Further evaluation of this role has been hampered by the lack of selective pharmacological inhibitors. Herein, we provide a comprehensive overview about the therapeutic potential of targeting CDK3 in cancer. Graphical Abstract: ga1