Role of Ink4a/Arf Locus in Beta Cell Mass Expansion under Physiological and Pathological Conditions
Figure 1
Mammalian cell cycle regulation. sequesters Cdk4 or Cdk6 inhibiting interactions with type D cyclins and preventing phosphorylation of pRB. Inactivation of CDK4/6 promotes Rb/E2F1 association triggering G1/S transition. Phosphorylation of pRB is essential for passage through the restriction point in G1. The cyclin D1-Cdk4 complex specifically phosphorylates the pRB protein leading to sequential phosphorylation by cyclin E-Cdk2 and release of free E2F. The phosphorylation of pRB, and relief of transcriptional inhibition by pRB induces S-phase entry. p53-dependent regulation by p21 and p27 contributes to checkpoint maintenance at later timepoints. Cdc2-Cyclin A/B binding contribute to phosphorylation of proteins involved in G2/M transition.
