The RB pathway functions primarily through the interaction between pRB and E2F transcription factors. In its active form, pRB binds to E2F, inhibiting the transcription of genes required for DNA replication. When cells receive signals to proliferate, cyclin-dependent kinases (CDKs) phosphorylate pRB, causing it to release E2F. This release allows E2F to activate genes necessary for the S phase, thus promoting cell cycle progression.