p53 Phosphorylation and Association with Murine Double Minute 2, c-Jun NH2-Terminal Kinase, p14ARF, and p300/CBP during the Cell Cycle and after Exposure to Ultraviolet Irradiation
2000
p53 phosphorylation and association with proteins is implicated in its
stability and activity. We have compared the association of DNA-bound
and overall pools of p53 with murine double minute 2 (Mdm2), c-Jun
NH 2 -terminal kinase (JNK), p300/CBP, and p14 ARF
during cell cycle progression. Whereas DNA-bound p53 associates with
JNK at G 0 -G 1 and with Mdm2 and p300 during S
and G 2 -M phases, the general pool of p53 was found in
complex with JNK and Mdm2 almost throughout the cell cycle.
Phosphorylation of p53 at serines 9, 15, and 20 is at the highest
levels at G 1 and at serines 37 and 392 during
G 2 -M phase. Whereas a high dose of UV irradiation was
required for phosphorylation of serines 15 and 392 between 8 and
24 h after treatment, a low dose caused immediate phosphorylation
on serines 9, 20, and 372. These dynamic changes in the phosphorylation
of p53 are expected to play a pivotal role in p53 association,
stability, and function.
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