PMID- 10446957
OWN - NLM
STAT- MEDLINE
DCOM- 19990907
LR  - 20131121
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 59
IP  - 15
DP  - 1999 Aug 1
TI  - Enhanced phosphorylation of p53 serine 18 following DNA damage in DNA-dependent
      protein kinase catalytic subunit-deficient cells.
PG  - 3543-6
AB  - DNA-dependent protein kinase (DNA-PK) controls signal transduction following DNA 
      damage. However, the molecular mechanism of the signal transduction has been
      elusive. A number of candidates for substrates of DNA-PK have been reported on
      the basis of the in vitro assay system. In particular, the Ser-15 amino acid
      residue in p53 was one of the first such in vitro substrates to be described, and
      it has drawn considerable attention due to its biological significance. Moreover,
      p53 Ser-15 is a site that has been shown to be phosphorylated in response to DNA 
      damage. In addition, crucial evidence indicating that DNA-PK controls the
      transactivation of p53 following DNA damage was reported quite recently. To
      clarify these important issues, we conducted the experiments with dna-pkcs null
      mutant cells, including gene knockout cells. As a result, we detected enhanced
      phosphorylation of p53 Ser-18, which corresponds to Ser-15 of human p53, and
      significant expression of p21 and mdm2 following ionizing radiation. Furthermore,
      we identified a missense point mutation in the p53 DNA-binding motif region in
      SCGR11 cells, which were established from severe combined immunodeficient (SCID) 
      mice and used for previous study on the role of DNA-PK in p53 transactivation.
      Our observation clearly indicates that DNA-PK catalytic subunit does not
      phosphorylate p53 Ser-18 in vivo or control the transactivation of p53 in
      response to DNA damage, and these results further emphasize the different
      pathways in which ataxia telangiectasia-mutated (ATM) and DNA-PK operate
      following radiation damage.
FAU - Araki, R
AU  - Araki R
AD  - National Institute of Radiological Sciences, Chiba, Japan.
FAU - Fukumura, R
AU  - Fukumura R
FAU - Fujimori, A
AU  - Fujimori A
FAU - Taya, Y
AU  - Taya Y
FAU - Shiloh, Y
AU  - Shiloh Y
FAU - Kurimasa, A
AU  - Kurimasa A
FAU - Burma, S
AU  - Burma S
FAU - Li, G C
AU  - Li GC
FAU - Chen, D J
AU  - Chen DJ
FAU - Sato, K
AU  - Sato K
FAU - Hoki, Y
AU  - Hoki Y
FAU - Tatsumi, K
AU  - Tatsumi K
FAU - Abe, M
AU  - Abe M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Proteins)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 17885-08-4 (Phosphoserine)
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 (Atm protein, mouse)
RN  - EC 2.7.11.1 (DNA-Activated Protein Kinase)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Ataxia Telangiectasia Mutated Proteins
MH  - Binding Sites
MH  - Cell Cycle Proteins
MH  - Cells, Cultured
MH  - *DNA Damage
MH  - DNA-Activated Protein Kinase
MH  - *DNA-Binding Proteins
MH  - Fibroblasts/radiation effects
MH  - Gene Targeting
MH  - Mammary Neoplasms, Experimental/pathology
MH  - Mice
MH  - Mice, SCID
MH  - Phosphorylation
MH  - Phosphoserine/*metabolism
MH  - Protein Biosynthesis
MH  - *Protein Processing, Post-Translational
MH  - Protein-Serine-Threonine Kinases/chemistry/deficiency/genetics/*physiology
MH  - Proteins/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tumor Cells, Cultured/radiation effects
MH  - Tumor Suppressor Protein p53/*metabolism
MH  - Tumor Suppressor Proteins
EDAT- 1999/08/14 00:00
MHDA- 1999/08/14 00:01
CRDT- 1999/08/14 00:00
PHST- 1999/08/14 00:00 [pubmed]
PHST- 1999/08/14 00:01 [medline]
PHST- 1999/08/14 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1999 Aug 1;59(15):3543-6.