Figure 1.

Classical view of the RB pathway and RB function in mammalian cells. (A) Schematic representation of the canonical RB pathway. Small cell cycle inhibitors prevent the phosphorylation of RB and its family members by Cyclin/Cdk complexes. E2F transcription factors are major mediators of RB function in mammalian cells. (B) Examples of RB's mode of action in cells to restrain cell cycle progression and promote differentiation. (Top) Classically, RB binds to the regulatory regions of cell cycle genes via its interaction with E2F transcription factors and recruits repressor complexes to inhibit the expression of cell cycle genes. (Second from top) RB also controls the cell cycle by blocking the degradation of the p27 small cell cycle inhibitor (of the p21 family) by Skp2; high p27 levels can directly inhibit Cdk2 kinase activity and slow cell cycle progression. (Third from top) RB can promote differentiation in cooperation with other transcription factors, such as Runx2, in the bone lineage. (Bottom) RB can also control cell fate by controlling the expression of transcription factors involved in cellular differentiation, such as PPARγ during adipogenesis.