PMID- 10347217
OWN - NLM
STAT- MEDLINE
DCOM- 19990701
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 23
DP  - 1999 Jun 4
TI  - Oligomerization is required for p53 to be efficiently ubiquitinated by MDM2.
PG  - 16531-5
AB  - Wild-type p53 is degraded in part through the ubiquitin proteolysis pathway.
      Recent studies indicate that MDM2 can bind p53 and promote its rapid degradation 
      although the molecular basis for this degradation has not been clarified. This
      report demonstrates that MDM2 can promote the ubiquitination of wild-type p53 and
      cancer-derived p53 mutants in transiently transfected cells. Deletion mutants
      that disrupted the oligomerization domain of p53 displayed low binding affinity
      for MDM2 and were poor substrates for ubiquitination. However, efficient MDM2
      binding and ubiquitination were restored when an oligomerization-deficient p53
      mutant was fused to the dimerization domain from another protein. These results
      indicate that oligomerization is required for p53 to efficiently bind and be
      ubiquitinated by MDM2. p53 ubiquitination was inhibited in cells exposed to UV
      radiation, and this inhibition coincided with a decrease in MDM2 protein levels
      and p53.MDM2 complex formation. In contrast, p53 dimerization was unaffected
      following UV treatment. These results suggest that UV radiation may stabilize p53
      by blocking the ubiquitination and degradation of p53 mediated by MDM2.
FAU - Maki, C G
AU  - Maki CG
AD  - Harvard School of Public Health, Department of Cancer Cell Biology, Boston,
      Massachusetts 02115, USA. cmaki@hsph.harvard.edu
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (Ubiquitins)
RN  - EC 2.3.2.27 (MDM2 protein, human)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2)
SB  - IM
MH  - Humans
MH  - *Nuclear Proteins
MH  - Point Mutation
MH  - Protein Conformation
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-mdm2
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Protein p53/genetics/*metabolism/radiation effects
MH  - Ubiquitins/metabolism
MH  - Ultraviolet Rays
MH  - *Zinc Fingers
EDAT- 1999/05/29 00:00
MHDA- 1999/05/29 00:01
CRDT- 1999/05/29 00:00
PHST- 1999/05/29 00:00 [pubmed]
PHST- 1999/05/29 00:01 [medline]
PHST- 1999/05/29 00:00 [entrez]
AID - 10.1074/jbc.274.23.16531 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jun 4;274(23):16531-5. doi: 10.1074/jbc.274.23.16531.