PMID- 10601022
OWN - NLM
STAT- MEDLINE
DCOM- 20000127
LR  - 20161124
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 18
IP  - 24
DP  - 1999 Dec 15
TI  - Serine15 phosphorylation stimulates p53 transactivation but does not directly
      influence interaction with HDM2.
PG  - 7002-10
AB  - The p53 tumour suppressor protein is a labile transcription factor that is
      activated and stabilized in response to a wide range of cellular stresses,
      through a mechanism involving disruption of its interaction with MDM2, a negative
      regulatory partner. Induction of p53 by DNA damage additionally involves a series
      of phosphorylation and acetylation modifications, some of which are thought to
      regulate MDM2 binding. Here we report the effects of introducing mutations at
      several known or putative N-terminal phosphorylation sites on the transactivation
      function of p53. These studies highlight phosphorylation of Ser15, a key
      phosphorylation target during the p53 activation process, as being critical for
      p53-dependent transactivation. Biochemical data indicate that the mechanism by
      which phosphorylation of Ser15 stimulates p53-dependent transactivation occurs
      through increased binding to the p300 coactivator protein. The data also indicate
      that Ser15-dependent regulation of transactivation is independent of any
      involvement in modulating MDM2 binding, and that Ser15 phosphorylation alone is
      not sufficient to block the p53-MDM2 interaction.
FAU - Dumaz, N
AU  - Dumaz N
AD  - Biomedical Research Centre, Ninewells Hospital and Medical School, University of 
      Dundee, Dundee DD1 9SY, UK.
FAU - Meek, D W
AU  - Meek DW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Recombinant 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)
RN  - EC 2.7.11.1 (DNA-Activated Protein Kinase)
RN  - EC 2.7.11.1 (PRKDC protein, human)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
SB  - IM
MH  - Amino Acid Substitution
MH  - Cell Line
MH  - DNA-Activated Protein Kinase
MH  - *DNA-Binding Proteins
MH  - Genes, Reporter
MH  - Humans
MH  - Mutagenesis, Site-Directed
MH  - *Nuclear Proteins
MH  - Phosphoserine/metabolism
MH  - Protein-Serine-Threonine Kinases/*metabolism
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-mdm2
MH  - Recombinant Fusion Proteins/metabolism
MH  - Recombinant Proteins/metabolism
MH  - *Serine
MH  - Transcriptional Activation
MH  - Transfection
MH  - Tumor Suppressor Protein p53/*chemistry/*metabolism
PMC - PMC1171763
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 - 10.1093/emboj/18.24.7002 [doi]
PST - ppublish
SO  - EMBO J. 1999 Dec 15;18(24):7002-10. doi: 10.1093/emboj/18.24.7002.