A novel CCAAT-binding protein necessary for adhesion-dependent cyclin A transcription at the G1/S boundary is sequestered by a retinoblastoma-like protein in G0.
Loss of adhesion leads to cell cycle arrest at the G1/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 G1 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 G0-arrested or nonadherent normal rat kidney fibroblasts. During G0 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 G1/S boundary, is regulated by CBP/cycA and the phosphorylation status of the retinoblastoma protein or a retinoblastoma-related protein.
Krämer
A
A
McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, Wisconsin 53706, USA.
Carstens
C P
CP
Fahl
W E
WE
D000818:Animals; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D002478:Cells, Cultured; D016213:Cyclins / Q000235:genetics*; D004247:DNA; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016193:G1 Phase; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051381:Rats; D016192:Resting Phase, Cell Cycle; D016160:Retinoblastoma Protein / Q000378:metabolism*; D016196:S Phase; D014158:Transcription, Genetic
D022762:CCAAT-Enhancer-Binding Proteins; D016213:Cyclins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D016160:Retinoblastoma Protein; D004247:DNA