Interaction between YY1 and the retinoblastoma protein - Regulation of cell cycle progression in differentiated cells

Overexpression of the transcription factor YY1 activates DNA synthesis in d ifferentiated primary human coronary artery smooth muscle cells. Overexpres sion of the retinoblastoma protein together with YY1 blocked this effect. I n growth-arrested cells, YY1 resides in a complex with the retinoblastoma p rotein, but the complex is not detected in serum-stimulated S phase culture s, indicating that the interaction of the retinoblastoma protein and YY1 is cell cycle-regulated. Recombinant retinoblastoma protein directly interact s with YY1, destabilizing the interaction of YY1 with DNA and inhibiting it s transcription initiator function in vitro. We conclude that in differenti ated cells elevation of the nuclear level of YY1 protein favors progression into the S phase, and we propose that this activity is regulated by its in teraction with the retinoblastoma protein.