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. 2024 Jan 19;25(2):1242. doi: 10.3390/ijms25021242

Figure 1.

Figure 1

Cyclin-CDK-E2F-Rb pathway with estrogen signaling resulting in amplification of cyclin D is shown. In box 1, estrogen (E2) binds with estrogen receptor (ER) and is translocated to the nucleus, where it, then promotes the transcription of the CCND1 gene resulting in cyclin D1. Pro-mitogenic signals and other pathways can also amplify cyclin D1 transcription, which is discussed elsewhere. In box 2, cyclin D1 then binds with cyclin-dependent kinase (CDK) 4 and 6 to create an activated holoenzyme. In box 3, this cyclin-CDK 4/6 complex phosphorylates retinoblastoma protein (Rb), which results in the dissociation of Rb from the E2F transcription factor seen in box 4. In box 5, the now free E2F transcription factor promotes the downstream cascade of protein synthesis, ultimately transitioning the cell from G1 to S phase. Further, E2F transcribes the CDK2NA gene, which results in the synthesis of p16INK4a, a potent inhibitor of the cyclin-CDK 4/6 complex. This results in a negative feedback loop, which arrests the progression of the cell cycle.