PMID- 10597229
OWN - NLM
STAT- MEDLINE
DCOM- 20000110
LR  - 20161124
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 46
DP  - 1999 Nov 4
TI  - Dephosphorylation of p53 at Ser20 after cellular exposure to low levels of
      non-ionizing radiation.
PG  - 6305-12
AB  - Induction of the transactivation function of p53 after cellular irradiation was
      studied under conditions in which upstream signaling events modulating p53
      activation were uncoupled from those regulating stabilization. This investigation
      prompted the discovery of a novel radiation-responsive kinase pathway targeting
      Ser20 that results in the masking of the DO-1 epitope in undamaged cells.
      Unmasking of the DO-1 epitope via dephosphorylation occurs in response to low
      doses of non-ionizing radiation. Our data show that phosphorylation at Ser20
      reduces binding of the mdm2 protein, suggesting that a function of the
      Ser20-kinase pathway may be to produce a stable pool of inactive p53 in undamaged
      cells which can be readily activated after cellular injury. Phospho-specific
      monoclonal antibodies were used to determine whether the Ser20 signaling pathway 
      is coupled to the Ser15 and Ser392 radiation-responsive kinase pathways. These
      results demonstrated that: (1) dephosphorylation at Ser20 is co-ordinated with an
      increased steady-state phosphorylation at Ser392 after irradiation, without p53
      protein stabilization, and (2) stabilization of p53 protein can occur without
      Ser15 phosphorylation at higher doses of radiation. These data show that the
      Ser20 and Ser392 phosphorylation sites are both targeted by an integrated network
      of signaling pathways which is acutely sensitive to radiation injury.
FAU - Craig, A L
AU  - Craig AL
AD  - Department of Molecular and Cellular Pathology, Dundee Cancer Research Institute,
      University of Dundee, Scotland, UK.
FAU - Blaydes, J P
AU  - Blaydes JP
FAU - Burch, L R
AU  - Burch LR
FAU - Thompson, A M
AU  - Thompson AM
FAU - Hupp, T R
AU  - Hupp TR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Epitopes)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 17885-08-4 (Phosphoserine)
RN  - 452VLY9402 (Serine)
RN  - EC 2.3.2.27 (MDM2 protein, human)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2)
SB  - IM
MH  - Antibodies, Monoclonal/immunology
MH  - Breast Neoplasms/chemistry/immunology/pathology
MH  - Epitopes/metabolism
MH  - Female
MH  - Humans
MH  - *Nuclear Proteins
MH  - Phosphorylation/radiation effects
MH  - Phosphoserine/*chemistry/immunology
MH  - Protein Processing, Post-Translational/*radiation effects
MH  - Protein Structure, Tertiary
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-mdm2
MH  - Serine/*chemistry
MH  - Signal Transduction/radiation effects
MH  - Transcriptional Activation/*radiation effects
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Protein p53/immunology/*metabolism
MH  - *Ultraviolet Rays
EDAT- 1999/12/22 00:00
MHDA- 1999/12/22 00:01
CRDT- 1999/12/22 00:00
PHST- 1999/12/22 00:00 [pubmed]
PHST- 1999/12/22 00:01 [medline]
PHST- 1999/12/22 00:00 [entrez]
AID - 10.1038/sj.onc.1203085 [doi]
PST - ppublish
SO  - Oncogene. 1999 Nov 4;18(46):6305-12. doi: 10.1038/sj.onc.1203085.