PMID- 10373484
OWN - NLM
STAT- MEDLINE
DCOM- 19990715
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 26
DP  - 1999 Jun 25
TI  - p73 and p63 are homotetramers capable of weak heterotypic interactions with each 
      other but not with p53.
PG  - 18709-14
AB  - Mutations in the p53 tumor suppressor gene are the most frequent genetic
      alterations found in human cancers. Recent identification of two human homologues
      of p53 has raised the prospect of functional interactions between family members 
      via a conserved oligomerization domain. Here we report in vitro and in vivo
      analysis of homo- and hetero-oligomerization of p53 and its homologues, p63 and
      p73. The oligomerization domains of p63 and p73 can independently fold into
      stable homotetramers, as previously observed for p53. However, the
      oligomerization domain of p53 does not associate with that of either p73 or p63, 
      even when p53 is in 15-fold excess. On the other hand, the oligomerization
      domains of p63 and p73 are able to weakly associate with one another in vitro. In
      vivo co-transfection assays of the ability of p53 and its homologues to activate 
      reporter genes showed that a DNA-binding mutant of p53 was not able to act in a
      dominant negative manner over wild-type p73 or p63 but that a p73 mutant could
      inhibit the activity of wild-type p63. These data suggest that mutant p53 in
      cancer cells will not interact with endogenous or exogenous p63 or p73 via their 
      respective oligomerization domains. It also establishes that the multiple
      isoforms of p63 as well as those of p73 are capable of interacting via their
      common oligomerization domain.
FAU - Davison, T S
AU  - Davison TS
AD  - Ontario Cancer Institute and Department of Medical Biophysics, University of
      Toronto, Toronto, Ontario M5G 2M9, Canada.
FAU - Vagner, C
AU  - Vagner C
FAU - Kaghad, M
AU  - Kaghad M
FAU - Ayed, A
AU  - Ayed A
FAU - Caput, D
AU  - Caput D
FAU - Arrowsmith, C H
AU  - Arrowsmith CH
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 (CKAP4 protein, human)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (TP63 protein, human)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Protein p73)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (p73 protein, human)
SB  - IM
MH  - Amino Acid Sequence
MH  - *Apoptosis
MH  - Blotting, Western
MH  - Circular Dichroism
MH  - DNA-Binding Proteins/*metabolism
MH  - Electrophoresis, Polyacrylamide Gel
MH  - *Genes, Tumor Suppressor
MH  - Humans
MH  - *Membrane Proteins
MH  - Molecular Sequence Data
MH  - Nuclear Proteins/*metabolism
MH  - Phosphoproteins/*metabolism
MH  - Protein Conformation
MH  - Protein Folding
MH  - Sequence Alignment
MH  - *Trans-Activators
MH  - Transcription Factors
MH  - *Transcriptional Activation
MH  - Tumor Protein p73
MH  - Tumor Suppressor Protein p53/*metabolism
MH  - Tumor Suppressor Proteins
EDAT- 1999/06/22 00:00
MHDA- 1999/06/22 00:01
CRDT- 1999/06/22 00:00
PHST- 1999/06/22 00:00 [pubmed]
PHST- 1999/06/22 00:01 [medline]
PHST- 1999/06/22 00:00 [entrez]
AID - 10.1074/jbc.274.26.18709 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jun 25;274(26):18709-14. doi: 10.1074/jbc.274.26.18709.