P202, AN INTERFERON-INDUCIBLE MODULATOR OF TRANSCRIPTION, INHIBITS TRANSCRIPTIONAL ACTIVATION BY THE P53 TUMOR-SUPPRESSOR PROTEIN, AND A SEGMENT FROM THE P53-BINDING PROTEIN-1 THAT BINDS TO P202 OVERCOMES THISINHIBITION

p202, an intel feron-inducible murine protein, is a member of the ''20 0 family'' of proteins and is primarily nuclear. p202 is a modulator o f transcription; it binds several transcription factors, including NF- kappa B p50 and p65, AP-1 c-Fos and c-Jun, and E2F1, and inhibits thei r transcriptional activity, p202 also binds pRb, the retinoblastoma pr otein, and if overexpressed it retards cell proliferation, Here we rep ort that using the yeast two-hybrid assay we found that p202 bound the murine homolog of the human p53-binding protein 1 (53BP1), a protein shown to interact with the DNA binding domain of the p53 tumor suppres sor protein. p202 bound a 98-amino acid segment from 53BP1. This bindi ng was inhibited by the replacement ill p202 of a histidine (from the M(F/L)HATVA(T/S) sequence that is conserved among all of the 200 famil y proteins) by phenylalanine. me also report that overexpression of p2 02 inhibited the p53-dependent expression of reporter genes containing p53-activable segments from the mdm2 and p21 genes, whereas a decreas e in the p202 level (in consequence of the expression of 202 antisense RNA) resulted in an increase in the p53-dependent expression of these reporters. Expression of the 53BP1 segment binding to p202 overcame t he inhibition by overexpressed p202 of the transcription of reporters mediated by the p53 or the AP-1 transcription factors and of the proli feration of yeast.