Regulation of E2F/cyclin A-containing complex upon retinoic acid-induced differentiation of teratocarcinoma cells.

Retinoic acid-induced differentiation of mouse P19 teratocarcinoma cells is accompanied by alterations in the level of E2F transcription factor. P19 stem cells contain free, uncomplexed E2F and an E2F complex termed E2F/stem. This stem cell complex is a heterotrimeric protein aggregate consisting of E2F transcription factor, E2F-binding protein (E2F/bp1), and cyclin A. Retinoic acid treatment converts P19 stem cells into differentiated neurons, glial cells, and fibroblasts. The presented experiments clearly show that the level of uncomplexed E2F gradually decreases upon differentiation, and fully differentiated cells do not contain free E2F. In addition, the stem cell-specific E2F aggregate is converted into a smaller complex, termed E2F/diff. This smaller complex, which is specific for differentiated cells, does not contain cyclin A and consists of E2F transcription factor associated with E2F/bp1. Finally, the role of E2F complexes in the cessation of cell proliferation, which accompanies P19 cell differentiation, is discussed.