PMID- 10656682
OWN - NLM
STAT- MEDLINE
DCOM- 20000210
LR  - 20131121
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 19
IP  - 3
DP  - 2000 Jan 20
TI  - Cooperative phosphorylation at multiple sites is required to activate p53 in
      response to UV radiation.
PG  - 358-64
AB  - The activity of the tumor suppressor p53 is induced in response to DNA-damaging
      agents such as UV and gamma radiation. Phosphorylation is one of the key
      regulatory steps for activating p53 function. Recent reports have shown that p53 
      is phosphorylated at both serines 15 and 392 in response to UV radiation.
      Phosphorylation at serine 15 prevents the binding of HDM2, a negative regulator
      of p53. Phosphorylation at serine 392 induces the DNA-binding function of p53. We
      examined the requirement for phosphorylation at both serines and show that both
      these modifications occur on the same molecule of p53. In vitro assays
      demonstrate that phosphorylation at either one of these sites is not sufficient
      to yield an active p53. Phosphorylation by DNA-PK, that modifies serines 15 and
      37, inhibits HDM2 binding to p53 but does not induce the DNA-binding activity of 
      p53. Phosphorylation at serine 392, on the other hand, stimulates the DNA-binding
      ability of p53 but does not make it immune to binding and inhibition by HDM2.
      Thus, our results demonstrate that multiple sites need to be modified to yield a 
      functional p53.
FAU - Kapoor, M
AU  - Kapoor M
AD  - Department of Molecular Genetics, MD Anderson Cancer Center, Houston, Texas
      77030, USA.
FAU - Hamm, R
AU  - Hamm R
FAU - Yan, W
AU  - Yan W
FAU - Taya, Y
AU  - Taya Y
FAU - Lozano, G
AU  - Lozano G
LA  - eng
GR  - CA47296/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 452VLY9402 (Serine)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.11.1 (Casein Kinase II)
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  - Casein Kinase II
MH  - Cell Line
MH  - DNA/metabolism
MH  - DNA-Activated Protein Kinase
MH  - *DNA-Binding Proteins
MH  - Humans
MH  - Nuclear Proteins
MH  - Phosphorylation
MH  - Protein-Serine-Threonine Kinases/physiology
MH  - Serine/metabolism
MH  - Tumor Suppressor Protein p53/*metabolism/radiation effects
MH  - *Ultraviolet Rays
EDAT- 2000/02/03 00:00
MHDA- 2000/02/03 00:01
CRDT- 2000/02/03 00:00
PHST- 2000/02/03 00:00 [pubmed]
PHST- 2000/02/03 00:01 [medline]
PHST- 2000/02/03 00:00 [entrez]
AID - 10.1038/sj.onc.1203300 [doi]
PST - ppublish
SO  - Oncogene. 2000 Jan 20;19(3):358-64. doi: 10.1038/sj.onc.1203300.