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(Received for publication, July 3, 1996, and in revised form, July 31, 1996)
From the p202, an interferon-inducible murine protein, is
a member of the ``200 family'' of proteins and is primarily nuclear.
p202 is a modulator of transcription; it binds several transcription
factors, including NF-
Volume 271, Number 44,
Issue of November 1, 1996
pp. 27544-27555
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
,
,
and
Department of Molecular Biophysics and
Biochemistry, Yale University, New Haven, Connecticut 06520, the
§ Department of Biochemistry and Cell Biology, State
University of New York, Stony Brook, New York 11794, and the
Boyer Center of Molecular Medicine and the Department of
Genetics, Yale University School of Medicine,
New Haven, Connecticut 06520
B p50 and p65, AP-1 c-Fos and c-Jun, and E2F1,
and inhibits their transcriptional activity. p202 also binds pRb, the
retinoblastoma protein, and if overexpressed it retards cell
proliferation. Here we report 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 suppressor protein. p202 bound a 98amino
acid segment from 53BP1. This binding was inhibited by the replacement
in p202 of a histidine (from the M(F/L)HATVA(T/S) sequence that is
conserved among all of the 200 family proteins) by phenylalanine. We
also report that overexpression of p202 inhibited the
p53-dependent expression of reporter genes containing
p53-activable segments from the mdm2 and p21
genes, whereas a decrease 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 the inhibition by
overexpressed p202 of the transcription of reporters mediated by the
p53 or the AP-1 transcription factors and of the proliferation of
yeast.
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