A Novel CCAAT-binding Protein Necessary for Adhesion-dependent Cyclin A Transcription at the G/S Boundary Is Sequestered by a Retinoblastoma-like Protein in G

Loss of adhesion leads to cell cycle arrest at the G /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 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 -arrested or nonadherent normal rat kidney fibroblasts. During G 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 /S boundary, is regulated by CBP/ cycA and the phosphorylation status of the retinoblastoma protein or a retinoblastoma-related protein.