PMID- 10082548
OWN - NLM
STAT- MEDLINE
DCOM- 19990420
LR  - 20190508
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 4
DP  - 1999 Apr
TI  - Requirement of ATM in phosphorylation of the human p53 protein at serine 15
      following DNA double-strand breaks.
PG  - 2828-34
AB  - Microinjection of the restriction endonuclease HaeIII, which causes DNA
      double-strand breaks with blunt ends, induces nuclear accumulation of p53 protein
      in normal and xeroderma pigmentosum (XP) primary fibroblasts. In contrast, this
      induction of p53 accumulation is not observed in ataxia telangiectasia (AT)
      fibroblasts. HaeIII-induced p53 protein in normal fibroblasts is phosphorylated
      at serine 15, as determined by immunostaining with an antibody specific for
      phosphorylated serine 15 of p53. This phosphorylation correlates well with p53
      accumulation. Treatment with lactacystin (an inhibitor of the proteasome) or heat
      shock leads to similar levels of p53 accumulation in normal and AT fibroblasts,
      but the p53 protein lacks a phosphorylated serine 15. Following microinjection of
      HaeIII into lactacystin-treated normal fibroblasts, lactacystin-induced p53
      protein is phosphorylated at serine 15 and stabilized even in the presence of
      cycloheximide. However, neither stabilization nor phosphorylation at serine 15 is
      observed in AT fibroblasts under the same conditions. These results indicate the 
      significance of serine 15 phosphorylation for p53 stabilization after DNA
      double-strand breaks and an absolute requirement for ATM in this phosphorylation 
      process.
FAU - Nakagawa, K
AU  - Nakagawa K
AD  - Institute of Molecular Embryology and Genetics, Kumamoto University School of
      Medicine, Kumamoto 862-0976, Japan.
FAU - Taya, Y
AU  - Taya Y
FAU - Tamai, K
AU  - Tamai K
FAU - Yamaizumi, M
AU  - Yamaizumi M
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Cysteine Proteinase Inhibitors)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (Proteins)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 133343-34-7 (lactacystin)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.11.1 (ATM protein, human)
RN  - EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 3.1.21.4 (Deoxyribonucleases, Type II Site-Specific)
RN  - EC 3.1.21.4 (GGCC-specific type II deoxyribonucleases)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/analogs & derivatives/pharmacology
MH  - Ataxia Telangiectasia/*metabolism
MH  - Ataxia Telangiectasia Mutated Proteins
MH  - Cell Cycle Proteins
MH  - Cysteine Endopeptidases/metabolism
MH  - Cysteine Proteinase Inhibitors/pharmacology
MH  - DNA Damage/*physiology
MH  - DNA-Binding Proteins
MH  - Deoxyribonucleases, Type II Site-Specific/metabolism
MH  - Heat-Shock Response
MH  - Humans
MH  - Multienzyme Complexes/metabolism
MH  - Phosphorylation
MH  - Proteasome Endopeptidase Complex
MH  - *Protein-Serine-Threonine Kinases
MH  - Proteins/*metabolism
MH  - Serine/*metabolism
MH  - Tumor Suppressor Protein p53/*metabolism
MH  - Tumor Suppressor Proteins
MH  - Xeroderma Pigmentosum/metabolism
PMC - PMC84075
EDAT- 1999/03/19 00:00
MHDA- 1999/03/19 00:01
CRDT- 1999/03/19 00:00
PHST- 1999/03/19 00:00 [pubmed]
PHST- 1999/03/19 00:01 [medline]
PHST- 1999/03/19 00:00 [entrez]
AID - 10.1128/mcb.19.4.2828 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 Apr;19(4):2828-34. doi: 10.1128/mcb.19.4.2828.