Regulation of the RB pathway is primarily achieved through phosphorylation by cyclin-dependent kinases (CDKs). Cyclin D-CDK4/6 complexes initiate the phosphorylation of RB, leading to its inactivation. This inactivation releases E2F transcription factors, allowing the transcription of S phase-promoting genes. Conversely, CDK inhibitors such as p16INK4a can bind to CDK4/6, preventing RB phosphorylation and thus maintaining its tumor suppressor function.
