PMID- 10608892
OWN - NLM
STAT- MEDLINE
DCOM- 20000208
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 53
DP  - 1999 Dec 31
TI  - Stabilization of the MDM2 oncoprotein by interaction with the structurally
      related MDMX protein.
PG  - 38189-96
AB  - The MDM2 oncoprotein has transforming potential that can be activated by
      overexpression, and it represents a critical regulator of the p53 tumor
      suppressor protein. To identify other factors with a potential role in
      influencing the expression and/or function of MDM2, we utilized a yeast
      two-hybrid screening protocol. Here we report that MDM2 physically interacts with
      a structurally related protein termed MDMX. The results obtained in these studies
      provide evidence that C-terminal RING finger domains, contained within both of
      these proteins, play an important role in mediating the association between MDM2 
      and MDMX. The interaction of these proteins interferes with MDM2 degradation,
      leading to an increase in the steady-state levels of MDM2. MDMX also inhibits
      MDM2-mediated p53 degradation, with subsequent accumulation of p53. Taken
      together, these data indicate that MDMX has the potential to regulate the
      expression and function of the MDM2 oncoprotein.
FAU - Sharp, D A
AU  - Sharp DA
AD  - Department of Genetics, University of Pennsylvania School of Medicine,
      Philadelphia, Pennsylvania 19104-6069, USA.
FAU - Kratowicz, S A
AU  - Kratowicz SA
FAU - Sank, M J
AU  - Sank MJ
FAU - George, D L
AU  - George DL
LA  - eng
GR  - CA-66741/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA Primers)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.3.2.27 (MDM2 protein, human)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2)
SB  - IM
MH  - Base Sequence
MH  - DNA Primers
MH  - Humans
MH  - *Nuclear Proteins
MH  - Protein Binding
MH  - Protein Conformation
MH  - Proto-Oncogene Proteins/chemistry/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-mdm2
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Protein p53/metabolism
MH  - Two-Hybrid System Techniques
EDAT- 1999/12/23 00:00
MHDA- 1999/12/23 00:01
CRDT- 1999/12/23 00:00
PHST- 1999/12/23 00:00 [pubmed]
PHST- 1999/12/23 00:01 [medline]
PHST- 1999/12/23 00:00 [entrez]
AID - 10.1074/jbc.274.53.38189 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Dec 31;274(53):38189-96. doi: 10.1074/jbc.274.53.38189.