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CDK4/6 targets the checkpoint that closely regulates cell cycle progression from G1 to S phase. D-cyclins, CDK4 and CDK6 are tasked with monitoring this checkpoint safeguarding appropriate cell division. When D-cyclins interact with CDK4/6, the result is a complex that removes the inhibitory signal monitoring this checkpoint, allowing progression of the cycle ending in unregulated division.
Cyclin D1 levels increase in response to estrogen receptor transcriptional activity and signaling transmitted via ERBB2/P13K/AKT/mTOR
D type cyclin (Cyclin D1) levels increase fostering the formation of a protein stabilized holoenzyme along with CDK4/6. Activation of CDK4/6 is followed by hyperphosphorylation of pRb (phosphorylated retinoblastoma-associated protein) allowing the phosphate-bound Rb to disengage, freeing E2F transcription factors to code for genes needed to advance the cell cycle through the checkpoint ending in cell cycle progression (G1 proceeds to S phase).
The result of this now unregulated checkpoint is unrestricted cell division providing the platform to support replication driving disease progression.