An overview of CDK3 in cancer: clinical significance and pharmacological implications

Theodosia Teo; Sara Kasirzadeh; Hugo Albrecht; Matthew J Sykes; Yuchao Yang; Shudong Wang

doi:10.1016/j.phrs.2022.106249

An overview of CDK3 in cancer: clinical significance and pharmacological implications

Pharmacol Res. 2022 Jun:180:106249. doi: 10.1016/j.phrs.2022.106249. Epub 2022 May 6.

Authors

Theodosia Teo¹, Sara Kasirzadeh¹, Hugo Albrecht¹, Matthew J Sykes¹, Yuchao Yang¹, Shudong Wang²

Affiliations

¹ Drug Discovery and Development, Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia.
² Drug Discovery and Development, Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia. Electronic address: shudong.wang@unisa.edu.au.

PMID: 35533805
DOI: 10.1016/j.phrs.2022.106249

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.

Keywords: AT7519 (PubChem CID: 11338033); BAY1000394 (PubChem CID: 45380979); CYC065 (PubChem CID: 24983461); Cancer; Cell cycle; Cyclin-dependent kinase; NU6102 (PubChem CID: 4566); Pharmacology; Purvalanol A (PubChem CID: 456214); R547 (PubChem CID: 6918852); RO-3306 (PubChem CID: 135400873); SNX9–1 (PubChem ID: 739323); TG02 (PubChem CID: 16739650); Targeted cancer therapy; Transcription; tamoxifen (PubChem CID: 2733526).

Publication types

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

MeSH terms

Animals
Cell Cycle
Cyclin D / metabolism
Cyclin-Dependent Kinase 3 / metabolism
Humans
Neoplasms* / drug therapy
Neoplasms* / metabolism
Phosphorylation

Substances

Cyclin D
CDK3 protein, human
Cyclin-Dependent Kinase 3