PMID- 10581258
OWN - NLM
STAT- MEDLINE
DCOM- 20000131
LR  - 20161019
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 18
IP  - 23
DP  - 1999 Dec 1
TI  - Phosphorylation of human p53 by p38 kinase coordinates N-terminal phosphorylation
      and apoptosis in response to UV radiation.
PG  - 6845-54
AB  - Components of the ras signaling pathway contribute to activation of cellular p53.
      In MCF-7 cells, p38 kinase activated p53 more effectively than other members of
      the ras pathway. p53 and p38 kinase exist in the same physical complex, and
      co-expression of p38 stabilized p53 protein. In vitro, p38 kinase phosphorylated 
      p53 at Ser33 and Ser46, a newly identified site. Mutation of these sites
      decreased p53-mediated and UV-induced apoptosis, and the reduction correlated
      with total abrogation of UV-induced phosphorylation on Ser37 and a significant
      decrease in Ser15 phosphorylation in mutant p53 containing alanine at Ser33 and
      Ser46. Inhibition of p38 activation after UV irradiation decreased
      phosphorylation of Ser33, Ser37 and Ser15, and also markedly reduced UV-induced
      apoptosis in a p53-dependent manner. These results suggest that p38 kinase plays 
      a prominent role in an integrated regulation of N-terminal phosphorylation that
      regulates p53-mediated apoptosis after UV radiation.
FAU - Bulavin, D V
AU  - Bulavin DV
AD  - Laboratory of Cell Biology, National Cancer Institute, National Institutes of
      Health, Bethesda, MD 20892, USA.
FAU - Saito, S
AU  - Saito S
FAU - Hollander, M C
AU  - Hollander MC
FAU - Sakaguchi, K
AU  - Sakaguchi K
FAU - Anderson, C W
AU  - Anderson CW
FAU - Appella, E
AU  - Appella E
FAU - Fornace, A J Jr
AU  - Fornace AJ Jr
LA  - eng
GR  - GM52825/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 452VLY9402 (Serine)
RN  - EC 2.3.1.28 (Chloramphenicol O-Acetyltransferase)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - OF5P57N2ZX (Alanine)
SB  - IM
MH  - Alanine/metabolism
MH  - Apoptosis/*radiation effects
MH  - Chloramphenicol O-Acetyltransferase/metabolism
MH  - DNA Damage
MH  - Flow Cytometry
MH  - Humans
MH  - Mitogen-Activated Protein Kinases/genetics/*metabolism
MH  - Mutagenesis, Site-Directed
MH  - Phosphorylation/radiation effects
MH  - Plasmids/metabolism
MH  - Serine/metabolism
MH  - Time Factors
MH  - Transcription, Genetic
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Protein p53/genetics/*metabolism
MH  - *Ultraviolet Rays
MH  - p38 Mitogen-Activated Protein Kinases
PMC - PMC1171747
EDAT- 1999/12/03 09:00
MHDA- 2001/03/28 10:01
CRDT- 1999/12/03 09:00
PHST- 1999/12/03 09:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1999/12/03 09:00 [entrez]
AID - 10.1093/emboj/18.23.6845 [doi]
PST - ppublish
SO  - EMBO J. 1999 Dec 1;18(23):6845-54. doi: 10.1093/emboj/18.23.6845.