A NOVEL CCAAT-BINDING PROTEIN NECESSARY FOR ADHESION-DEPENDENT CYCLIN-A TRANSCRIPTION AT THE G(1) S BOUNDARY IS SEQUESTERED BY A RETINOBLASTOMA-LIKE PROTEIN IN G(0)/

Loss of adhesion leads to cell cycle arrest at the G(1)/S boundary in normal, adhesion-dependent, mesenchymal cells. This arrest is accompan ied by the inability to produce cyclin A. Using deletional and mutatio nal analysis of the cyclin A promoter, we have identified a CCAAT elem ent that mediates the adhesion; dependent transcriptional activation o f cyclin A in late G, phase of the cell cycle, Specific binding of a n ovel 40/115-kDa heterodimeric protein complex, which we have named CBP /cycA, to this CCAAT element was detectable in growing but not in G(0) -arrested or nonadherent normal rat kidney fibroblasts, During G(0) CB P/cycA appears to be present but sequestered by a retinoblastoma famil y member. These results suggest that expression of cyclin A, which con trols cell cycle progression by adhesion at the G(1)/S boundary, is re gulated by CBP/cycA and the phosphorylation status of the retinoblasto ma protein dr a retino blastoma-related protein.