A novel CCAAT-binding protein necessary for adhesion-dependent cyclin A transcription at the G sub(1)/S boundary is sequestered by a retinoblastoma-like protein in G sub(0)

Loss of adhesion leads to cell cycle arrest at the G sub(1)/S boundary in normal, adhesion-dependent, mesenchymal cells. This arrest is accompanied by the inability to produce cyclin A. Using deletional and mutational analysis of the cyclin A promoter, we have identified a CCAAT element that mediates the adhesion-dependent transcriptional activation of cyclin A in late G sub(1) phase of the cell cycle. Specific binding of a novel 40/115-kDa heterodimeric protein complex, which we have named CBP/ cycA, to this CCAAT element was detectable in growing but not in G sub(0)-arrested or nonadherent normal rat kidney fibroblasts. During G sub(0) CBP/cycA appears to be present but sequestered by a retinoblastoma family member. These results suggest that expression of cyclin A, which controls cell cycle progression by adhesion at the G sub(1)/S boundary, is regulated by CBP/cycA and the phosphorylation status of the retinoblastoma protein or a retino-blastoma-related protein.