Cyclin-dependent kinase 3–cyclin E complex (CDK3–cyclin E)

Cyclin-dependent kinase 3–cyclin E is a heterodimeric serine/threonine kinase complex that plays a crucial role in regulating cell cycle transitions, especially the late G0–G1 and G1–S phases[3][4][8]. CDK3 is structurally related to CDK2 and is activated upon binding cyclin E, with the complex phosphorylating substrates including the retinoblastoma protein (RB), transcription factors such as E2F, c-JUN, and ATF1, thereby promoting cell cycle progression and proliferation. While the cyclin E–CDK2 pair is better studied, cyclin E–CDK3 appears to have nonredundant functions and can substitute for CDK2 in certain contexts. Aberrant activity or overexpression of cyclin E and CDK3 correlates with cancer development and poor prognosis in multiple malignancies[3][7]. Selective inhibition of this complex is a potential therapeutic strategy, but currently there are no marketed drugs specifically targeting CDK3–cyclin E. Safety challenges include on-target toxicity due to essential roles in proliferating normal tissues.

Other names

Cyclin E–CDK3CDK3/cyclin ECyclin-dependent kinase 3–cyclin E1 complex

Inhibition of the CDK3–cyclin E kinase activity blocks phosphorylation of RB and other substrates, leading to cell cycle arrest in G1. Disruption of complex formation or kinase activation may inhibit cell proliferation, especially in cancer cells reliant on abnormal CDK activity.