Question 1

What does CDK4 do in the cell cycle?

Accepted Answer

CDK4 forms complexes with D-type cyclins during G1 phase and phosphorylates the retinoblastoma protein (pRb), releasing E2F transcription factors to activate S-phase entry genes. This CDK4/cyclin D phosphorylation step is the G1 restriction point — the irreversible commitment to cell division.

Question 2

What drugs target CDK4?

Accepted Answer

CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) block the kinase active site, preventing pRb phosphorylation and reimposing G1 arrest. They are approved for hormone receptor-positive HER2-negative breast cancer and have extended median progression-free survival by more than a year in pivotal trials.

Question 3

What does CDK4 amplification mean in cancer?

Accepted Answer

CDK4 amplification on chromosome 12q13-15, often co-amplified with MDM2, leads to excessive pRb phosphorylation and unrestrained cell cycle entry. It is a key driver in well-differentiated and dedifferentiated liposarcoma, where CDK4 amplification is diagnostic and CDK4/6 inhibitors show activity.

CDK4 Gene Function

Overview

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