RB1 and neoplasm: Together with the retinoblastoma (Rb) protein tumor suppressor, and in parallel to p53 and p14ARF, p16INK4A and p15INK4B act at a checkpoint for human normal to tumor cell transformation, promoting cell cycle arrest, apoptosis, and senescence in response to rat sarcoma virus (Ras) -mediated hyperactive growth factor signaling [41–44].