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.
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 NH2-terminal kinase (JNK), p300/CBP, and p14ARF during cell cycle progression. Whereas DNA-bound p53 associates with JNK at G0-G1 and with Mdm2 and p300 during S and G2-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 G1 and at serines 37 and 392 during G2-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.
Buschmann
T
T
Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, New York 10029, USA.
Adler
V
V
Matusevich
E
E
Fuchs
S Y
SY
Ronai
Z
Z
D002453:Cell Cycle; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2; D015534:Trans-Activators / Q000378:metabolism*; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014466:Ultraviolet Rays
D009687:Nuclear Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases