N. Rolley et J. Milner, SPECIFIC DNA-BINDING BY P53 IS INDEPENDENT OF MUTATION AT SERINE-389,THE CASEIN KINASE-II SITE, Oncogene, 9(10), 1994, pp. 3067-3070
The best understood function of p53 is that of cell growth suppression
and this is likely to involve sequence-specific DNA binding and modul
ation of gene expression. Casein kinase II phosphorylates the C-termin
al serine of p53 (residue 389 for murine p53) and mutation of this sit
e abolishes p53 growth suppressor function. DNA binding by purified p5
3 is 'activated' by casein kinase II, suggesting that the carboxyl ter
minus of p53 represents a critical regulatory domain for sequence-spec
ific DNA binding and hence for growth suppressor function. In the pres
ent study we have substituted serine 389 with either aspartic acid (mi
mics phosphoserine and partially conserves p53 suppressor function) or
with alanine, a non-phosphorylable residue which abolishes suppressor
function (Milne et al., 1992; Nucleic Acids Research 20, 5565-5570).
When expressed in vitro p53(ala389) and p53(asp389) were both indistin
guishable from wild type p53 on the basis of size fractionation and im
munoreactivity with PAb421, PAb246 and PAb1620. Both mutants also exhi
bited specific binding for the DNA consensus p53-CON. Since p53(ala389
) retains the ability to bind DNA and yet is known to lack growth supp
ressor function we conclude that phosphorylation by casein kinase II i
s important for p53 growth suppressor function via a mechanism which i
s ancilliary to p53 sequence-specific DNA binding.