Multiple molecular interactions redundantly contribute to RB-mediated cell cycle control.

Background: The G1-S phase transition is critical to maintaining proliferative control and preventing carcinogenesis. The retinoblastoma tumor suppressor is a key regulator of this step in the cell cycle.

Results: Here we use a structure-function approach to evaluate the contributions of multiple protein interaction surfaces on pRB towards cell cycle regulation.

DNA damage signals through differentially modified E2F1 molecules to induce apoptosis.

E2F transcription can lead to cell proliferation or apoptosis, indicating that E2Fs control opposing functions. In a similar manner, DNA double-strand breaks can signal to induce cell cycle arrest or apoptosis. Specifically, pRB is activated following DNA damage, allowing it to bind to E2Fs and block transcription at cell cycle promoters; however, E2F1 is simultaneously activated, leading to transcription at proapoptotic promoters.