What is the role of Rb in the cell cycle and what types of mutations in Rb will be oncogenic? Explain your answer. Solution Cell cycle regulation by Rb: Gradual phosphorylation of Rb proteins causes their functional inactivation, which is regulated by cyclin dependent kinases. Rb proteins regulate the cell cycle in association with different transcription factors and chromatin-associated complexes. The transcription ability of E2F factors is inhibited by the binding of Rb proteins as they mask the transcriptional activation domain or convert them into transcription repressors. The two possible pathways through which Rb proteins mediate the inhibition of E2F regulated genes is, by direct binding to the activation domain and blocking it. The other one is, by repression through the HDAC , SWI/SNF factors or methyl transferases. As the retinoblastoma (Rb) is a tumour suppressor gene, so a loss of function mutation turns it to become oncogenic..