Nucleic Acids Research, Vol 24, Issue 6 1119-1126, Copyright © 1996 by Oxford University Press
SR Hall, LE Campbell and DW Meek
The p53 tumour suppressor protein is a potent transcription factor which
plays a central role in the defence of cells against DNA damage and the
propagation of malignant clones. We have previously shown that
phosphorylation of serine 386 in mouse p53 by the growth- associated
protein kinase, casein kinase II (CKII), plays an important role in the
ability of p53 to block the proliferation of drug-resistant colonies. In
this paper we show that blocking phosphorylation of serine 386 through an
alanine substitution, or placing a constitutive negative charge at this
position in the form of aspartate, had no significant influence on
p53-dependent transcriptional activation of a promoter containing 13 copies
of a p53 consensus binding sequence, or of the p21WAF1 promoter which is a
natural target for p53. In contrast, the alanine mutant showed a weak
reduction in the ability of p53 to repress expression from the c-fos
promoter, which is a target for p53-dependent repression in vivo.
Strikingly, when the repression of the SV40 early promoter was examined, a
reduction in the repression capacity of up to 5-fold was observed.
Moreover, repression of the SV40 promoter could be partially restored by
aspartic acid substitution at the phosphorylation site. These data indicate
that phosphorylation at a specific C-terminal site can selectively regulate
p53-dependent repression, but not transactivation.
ARTICLES
Phosphorylation of p53 at the casein kinase II site selectively regulates p53-dependent transcriptional repression but not transactivation
Biomedical Research Centre, University of Dundee, United Kingdom.
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