Cdk9 phosphorylates p53 on serine 392 independently of CKII

2006 ◽  
Vol 208 (3) ◽  
pp. 602-612 ◽  
Author(s):  
Pier Paolo Claudio ◽  
Jianqi Cui ◽  
Mohammad Ghafouri ◽  
Chiara Mariano ◽  
Martyn K. White ◽  
...  
Keyword(s):  
Serine 392

Human DNA-activated protein kinase phosphorylates serines 15 and 37 in the amino-terminal transactivation domain of human p53

1992 ◽  
Vol 12 (11) ◽  
pp. 5041-5049
Author(s):  
S P Lees-Miller ◽  
K Sakaguchi ◽  
S J Ullrich ◽  
E Appella ◽  
C W Anderson
Keyword(s):  
Protein Kinase ◽  
Synthetic Peptides ◽  
Wild Type Mouse ◽  
Tumor Suppressor Protein ◽  
Transactivation Domain ◽  
Wild Type ◽  
Amino Terminal ◽  
Human Dna ◽  
Serine 392 ◽  
P53 Peptides

Human DNA-PK is a nuclear, serine/threonine protein kinase that, when activated by DNA, phosphorylates several DNA-binding substrates, including the tumor suppressor protein p53. To identify which p53 residues are phosphorylated, we examined DNA-PK's ability to phosphorylate synthetic peptides corresponding to human p53 sequences. Serines 15 and 37 in the amino-terminal transactivation domain of human p53, and serines 7 and 18 of mouse p53, were phosphorylated by DNA-PK in the context of synthetic peptides. Other serines in these p53 peptides, and serines in other p53 peptides, including peptides containing the serine 315 p34cdc2 site and the serine 392 casein kinase II site, were not recognized by DNA-PK or were phosphorylated less efficiently. Phosphorylation of the conserved serine 15 in human p53 peptides depended on the presence of an adjacent glutamine, and phosphorylation was inhibited by the presence of a nearby lysine. Phosphorylation of recombinant wild-type mouse p53 was inhibited at high DNA concentrations, suggesting that DNA-PK may phosphorylate p53 only when both are bound to DNA at nearby sites. Our study suggests that DNA-PK may have a role in regulating cell growth and indicates how phosphorylation of serine 15 in DNA-bound p53 could alter p53 function.

scholarly journals Posttranslational Modifications of p53 in Replicative Senescence Overlapping but Distinct from Those Induced by DNA Damage

2000 ◽  
Vol 20 (8) ◽  
pp. 2803-2808 ◽  
Author(s):  
Katherine Webley ◽  
Jane A. Bond ◽  
Christopher J. Jones ◽  
Jeremy P. Blaydes ◽  
Ashley Craig ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Replicative Senescence ◽  
Human Fibroblasts ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Direct Role ◽  
Strand Breaks ◽  
Serine 392 ◽  
Regulatory Sites ◽  
Telomere Erosion

ABSTRACT Replicative senescence in human fibroblasts is absolutely dependent on the function of the phosphoprotein p53 and correlates with activation of p53-dependent transcription. However, no evidence for posttranslational modification of p53 in senescence has been presented, raising the possibility that changes in transcriptional activity result from upregulation of a coactivator. Using a series of antibodies with phosphorylation-sensitive epitopes, we now show that senescence is associated with major changes at putative regulatory sites in the N and C termini of p53 consistent with increased phosphorylation at serine-15, threonine-18, and serine-376 and decreased phosphorylation at serine-392. Ionizing and UV radiation generated overlapping but distinct profiles of response, with increased serine-15 phosphorylation being the only common change. These results support a direct role for p53 in signaling replicative senescence and are consistent with the generation by telomere erosion of a signal which shares some but not all of the features of DNA double-strand breaks.

scholarly journals The double-stranded RNA activated protein kinase PKR physically associates with the tumor suppressor p53 protein and phosphorylates human p53 on serine 392 in vitro

Oncogene ◽  
1999 ◽  
Vol 18 (17) ◽  
pp. 2690-2702 ◽  
Author(s):  
Andrew R Cuddihy ◽  
Andrew Hoi-Tao Wong ◽  
Nancy Wai Ning Tam ◽  
Suiyang Li ◽  
Antonis E Koromilas
Keyword(s):  
Protein Kinase ◽  
Tumor Suppressor ◽  
P53 Protein ◽  
Tumor Suppressor P53 ◽  
Double Stranded Rna ◽  
Serine 392

Prognostic Significance of Serine 392 Phosphorylation in Overexpressed p53 Protein in Human Esophageal Squamous Cell Carcinoma

Oncology ◽  
2004 ◽  
Vol 67 (2) ◽  
pp. 143-150 ◽  
Author(s):  
Manabu Matsumoto ◽  
Mutsuo Furihata ◽  
Atsushi Kurabayashi ◽  
Siro Sasaguri ◽  
Keijiro Araki ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
P53 Protein ◽  
Prognostic Significance ◽  
Serine 392

Benzo(a)pyrene increases phosphorylation of p53 at serine 392 in relation to p53 induction and cell death in MCF-7 cells

2008 ◽  
Vol 178 (3) ◽  
pp. 152-159 ◽  
Author(s):  
M. Tampio ◽  
J. Loikkanen ◽  
P. Myllynen ◽  
A. Mertanen ◽  
K.H. Vähäkangas
Keyword(s):  
Cell Death ◽  
Serine 392 ◽  
Mcf 7

scholarly journals Modification of serine 392 is a critical event in the regulation of p53 nuclear export and stability

FEBS Letters ◽  
2004 ◽  
Vol 572 (1-3) ◽  
pp. 92-98 ◽  
Author(s):  
Young-Youl Kim ◽  
Bum-Joon Park ◽  
Dong-Joon Kim ◽  
Woo-Hyang Kim ◽  
Soonhag Kim ◽  
...  
Keyword(s):  
Nuclear Export ◽  
Critical Event ◽  
Serine 392

Frequent phosphorylation at serine 392 in overexpressed p53 protein due to missense mutation in carcinoma of the urinary tract

2002 ◽  
Vol 197 (1) ◽  
pp. 82-88 ◽  
Author(s):  
Mutsuo Furihata ◽  
Atsushi Kurabayashl ◽  
Manabu Matsumoto ◽  
Hiroshi Sonobe ◽  
Yuji Ohtsuki ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Missense Mutation ◽  
P53 Protein ◽  
Serine 392

scholarly journals STING-mediated degradation of IFI16 negatively regulates apoptosis by inhibiting p53 phosphorylation at serine-392

2021 ◽  
pp. 100930
Author(s):  
Dapei Li ◽  
Lifen Xie ◽  
Zigang Qiao ◽  
Sanyue Mai ◽  
Jingfei Zhu ◽  
...  
Keyword(s):  
Serine 392

scholarly journals Changes in phosphorylation of histone H2A.X and p53 in response of peripheral blood lymphocytes to gamma irradiation.

2008 ◽  
Vol 55 (2) ◽  
pp. 381-390 ◽  
Author(s):  
Zdenka Vilasová ◽  
Martina Rezácová ◽  
Jirina Vávrová ◽  
Ales Tichý ◽  
Doris Vokurková ◽  
...  
Keyword(s):  
Gamma Radiation ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Kinase Inhibitor ◽  
Human Peripheral Blood ◽  
Dose Range ◽  
Dependent Manner ◽  
Pha Stimulation ◽  
Dose Dependent ◽  
Serine 392

The main aim of this study was to compare the reaction of quiescent and proliferating, i.e. phytohemagglutinin (PHA)-stimulated, human peripheral blood mononuclear cells (PBMCs) to gamma-radiation, and analyse changes of proteins related to repair of DNA damage and apoptosis, such as gammaH2A.X, p53, p53 phosphorylation at serines-15 and -392, and p21 and their dose dependence. Freshly isolated PBMCs in peripheral blood are predominantly quiescent, in G(0) phase, and with very low amounts of proteins p53 and p21. Using confocal microscopy we detected dose dependent (0.5-5 Gy) induction of foci containing gammaH2A.X (1 h after gamma-ray exposure), which are formed around radiation-induced double strand breaks of DNA. Apoptosis was detected from 24 h after irradiation by the dose of 4 Gy onwards by Annexin V binding and lamin B cleavage. Seventy two hours after irradiation 70% of CD3(+) lymphocytes were A(+). Neither increase in p53 nor its phosphorylation on serine-392 after irradiation was detected in these cells. However, massive increase in p21 (cyclin-dependent kinase inhibitor 1A) was detected after irradiation, which can be responsible for late occurrence of apoptosis in these quiescent cells. PHA-stimulation itself (72 h) caused an increase in early apoptosis (A(+)PI(-)) in comparison to non-stimulated PBMCs (38% A(+) resp. 13.4%). After PHA-stimulation also the amount of gammaH2A.X, p53, and p21 increased, but no phosphorylation of p53 on serine-392 or -15 was detected. Reaction to gamma-radiation was different in PHA-stimulated lymphocytes: the p53 pathway was activated and p53 was phosphorylated on serines-15 and -392 4 h after irradiation by the dose of 4 Gy. Phosphorylation of p53 at serine-15 increased in a dose-dependent manner in the studied dose range 0.2-7.5 Gy. Also the amount of p21 increased after irradiation. Seventy two hours after irradiation of PHA-stimulated CD3(+) T lymphocytes by the dose of 4 Gy 65% of cells were A(+).

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