TY - JOUR
T1 - Mutation of phosphoserine 389 affects p53 function in vivo
AU - Hao, Mingming
AU - Lowy, Andrew M.
AU - Kapoor, Mini
AU - Deffie, Abdul
AU - Liu, Geng
AU - Lozano, Guillermina
PY - 1996
Y1 - 1996
N2 - To study the importance of phosphorylation for p53 transactivation function, we generated mutations at each of its known phosphorylated serine amino acids. Mutations of murine p53 serine residues individually to either alanine or glutamic acid at positions 7, 9, 12, 18, 37, 312, and 389 resulted in equivalent levels of transcriptional activation in standard transient transfection experiments. However, when p53 transcriptional activity was measured in cells that attain G1 arrest upon contact inhibition, wild-type p53 was inactive, and only alteration at serine 389 to glutamic acid resulted in a functional p53 protein. This Ser → Glu mutant also has an increased ability to bind DNA. Elimination of the phosphorylation site by substitution of an alanine amino acid resulted in loss of transcriptional activity. We also demonstrated that specific phosphorylation of p53 at serine 389 is induced by cyclin E overexpression in high-density cells. Our data establish for the first time that phosphorylation of p53 at serine 389 is important in activating its function in vivo.
AB - To study the importance of phosphorylation for p53 transactivation function, we generated mutations at each of its known phosphorylated serine amino acids. Mutations of murine p53 serine residues individually to either alanine or glutamic acid at positions 7, 9, 12, 18, 37, 312, and 389 resulted in equivalent levels of transcriptional activation in standard transient transfection experiments. However, when p53 transcriptional activity was measured in cells that attain G1 arrest upon contact inhibition, wild-type p53 was inactive, and only alteration at serine 389 to glutamic acid resulted in a functional p53 protein. This Ser → Glu mutant also has an increased ability to bind DNA. Elimination of the phosphorylation site by substitution of an alanine amino acid resulted in loss of transcriptional activity. We also demonstrated that specific phosphorylation of p53 at serine 389 is induced by cyclin E overexpression in high-density cells. Our data establish for the first time that phosphorylation of p53 at serine 389 is important in activating its function in vivo.
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U2 - 10.1074/jbc.271.46.29380
DO - 10.1074/jbc.271.46.29380
M3 - Article
C2 - 8910602
AN - SCOPUS:0029825798
SN - 0021-9258
VL - 271
SP - 29380
EP - 29385
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 46
ER -