Multiple octamer-binding proteins are targets for the cell cycle-regulated nuclear inhibitor I-92.
p92 is a novel sequence-specific octamer-binding factor interacting with the enhancer of human papillomavirus type 18. The nuclear inhibitor I-92 regulates the DNA binding activity of p92 during the cell cycle such that p92 DNA binding is restricted to S-phase. The sequence motif ++ 5'-AATTGCTTGCATAA, consisting of two partially overlapping octamer-related sequences, represents a recognition site for p92. It was the aim of this study to characterize the complexity of proteins interacting with the 5'-AATTGCTTGCATAA motif and to determine their regulation by I-92. UV cross-linking experiments showed that, besides p92, multiple novel proteins interact with the 5'-AATTGCTGCATAA motif. These novel proteins p84, p75, p73, p69, p61, p57, p49, and p46 specifically bind to this motif, although with different affinities. The inhibitor I-92 regulates, besides p92, the DNA-binding activities of p84, p75, p73, p69, and p57 but not of p61, p49, and p46. The association of I-92 with p92, p84, p75, p73, p69, and p57 was completely reversible after treatment with the detergent deoxycholate (DOC). Finally, we analyzed I-92 specificity and found that I-92 selectively inhibited DNA binding activities of partially purified octamer-binding proteins p84 and p92 whereas DNA binding of the POU factor Oct-1 was not regulated by I-92. Our results show that I-92 regulates multiple octamer-binding proteins and these findings provide an example how gene regulation could be linked to cell cycle regulation.
Grinstein
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Max-Delbrück-Center for Molecular Medicine, Berlin-Buch, Germany.
Royer
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HD
D001483:Base Sequence; D001665:Binding Sites; D002453:Cell Cycle; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D016196:S Phase; D014157:Transcription Factors / Q000302:isolation & purification / Q000378:metabolism*
D004268:DNA-Binding Proteins; D014157:Transcription Factors