PMID- 10208433
OWN - NLM
STAT- MEDLINE
DCOM- 19990601
LR  - 20161124
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 9
DP  - 1999 Mar 4
TI  - DNA damage induced p53 stabilization: no indication for an involvement of p53
      phosphorylation.
PG  - 1723-32
AB  - Abundance and activity of p53 are predominantly regulated posttranslationally.
      Structural disturbance in transcribed genes induced by radiation, e.g. DNA
      damage, or by transcriptional inhibitors cause p53 protein stabilization by a yet
      unknown mechanism. Using stable and transient transfections for the analysis of
      p53 mutant proteins, we have ruled out a role in stabilization by UV, gamma
      irradiation or actinomycin C for the following putative phosphorylation sites in 
      the p53 protein: serines 6, 9, 15, 33, 315 and 392, and threonine 18. By double
      mutation combinations of phosphorylations were also ruled out; 6,9; 15,18; 15,37.
      These mutations eliminate modifications by casein kinases I and II, DNA-PK, ATM, 
      CDK and JNK. Also the 30 carboxyterminal amino acids are not required for induced
      p53 stabilization. Thus neither phosphorylations of individual amino acids nor
      interactions of the carboxyterminus of p53 with cellular macromolecules appear to
      play a role in the stabilization process. The only single prerequisite for
      induced stabilization of p53 is its prior destabilization by Mdm2. However, the
      level of active Mdm2 must be controlled carefully: overexpression of Mdm2
      inhibits UV induced p53 stabilization.
FAU - Blattner, C
AU  - Blattner C
AD  - Forschungszentrum Karlsruhe, Institut fur Genetik, Universitat Karlsruhe,
      Germany.
FAU - Tobiasch, E
AU  - Tobiasch E
FAU - Litfen, M
AU  - Litfen M
FAU - Rahmsdorf, H J
AU  - Rahmsdorf HJ
FAU - Herrlich, P
AU  - Herrlich P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.3.2.27 (Mdm2 protein, mouse)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Binding Sites
MH  - *DNA Damage
MH  - Gene Expression Regulation
MH  - Mice
MH  - *Nuclear Proteins
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-mdm2
MH  - Transcription, Genetic
MH  - Transfection
MH  - Tumor Suppressor Protein p53/genetics/*metabolism
EDAT- 1999/04/20 00:00
MHDA- 1999/04/20 00:01
CRDT- 1999/04/20 00:00
PHST- 1999/04/20 00:00 [pubmed]
PHST- 1999/04/20 00:01 [medline]
PHST- 1999/04/20 00:00 [entrez]
AID - 10.1038/sj.onc.1202480 [doi]
PST - ppublish
SO  - Oncogene. 1999 Mar 4;18(9):1723-32. doi: 10.1038/sj.onc.1202480.