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Figure 1. Positive and negative regulation of G1 progression by p21WAF1. p21WAF1 exerts a negative effect on G1 progression by inhibiting the activity of cyclin E/cdk2 complexes which phosphorylate pRb in mid to late G1 (1), as well as the function of PCNA in S phase (4). However, p21WAF1 can facilitate G1 phase progression as an assembly factor for cyclin D/cdk4 complexes (2). The induction of D-type cyclins in early G1 recruits p21WAF1 into these active cyclin D/cdk4 or cyclin D/cdk6 complexes, depleting the free pool of p21WAF1, and relieving the inhibition on cyclin E/cdk2 (3).
