"This is a very important step in the process of differentiation," Leone says. "As organs form during development, there comes a time when their growth must stop because an organ needs only a certain number of cells and no more. The switch by these proteins from activators to repressors is essential for that to happen. "Before this, there was no suspicion that these regulatory proteins had any role in differentiated cells," says Leone. "It was thought they were important only in proliferating cells like stem cells. But that's not true."

Leone and his colleagues show the function of the proteins in differentiation in mouse embryos, retinas, lenses and intestines.

They also show how the three proteins could revert back to gene activators in cancer cells and promote tumor growth in cancers with Rb mutations. "In this case, these proteins are acting abnormally relative to the surrounding tissue, so they might provide a safe therapeutic target," Leone explains. "If we can inactivate these E2fs in cancer cells, perhaps we can prevent further tumor growth without having a major affect on healthy cells."

Source: Ohio State University Medical Center