PMID- 10653977
OWN - NLM
STAT- MEDLINE
DCOM- 20000309
LR  - 20191024
IS  - 0730-2312 (Print)
IS  - 0730-2312 (Linking)
VI  - 76
IP  - 4
DP  - 2000 Jan
TI  - Function, oligomerization, and conformation of tumor-associated p53 proteins with
      mutated C-terminus.
PG  - 572-84
AB  - Mutations that affect the oligomerization domain (OD) of the p53 tumor suppressor
      may be of particular interest because of the remarkable contradiction between the
      conservation of the OD and its relative functional resistance to amino acid
      substitutions, and because of recent hints that cellular protein factors may
      interact with the OD. Both point to the possibility that this domain fulfills
      tasks beyond oligomerization. We report that the tumor-associated mutants 330H,
      334V, and 337C are defective for homo-oligomerization by three criteria.
      Accordingly, 330H and 337C failed to bind to a p53 recognition motif in gel-shift
      assays and to stimulate reporter genes efficiently in transient transfections.
      334V retained some activity in both assays despite being
      oligomerization-defective. The ability of the mutants to induce apoptosis
      correlated with their performance in the DNA binding and transactivation assays. 
      However, mutants 330H and 337C were able to provoke cell death when
      overexpressed, which in combination with their failure to transactivate genes
      suggests competence for the induction of transactivation-independent apoptosis at
      high protein levels. Although 334V and 337C failed to homo-oligomerize, they were
      able to hetero-oligomerize with a p53 with wild-type OD, and 334V was able to
      interfere with transactivation by wt p53. All mutants showed a reduced reactivity
      with antibody PAb421 and a distinct calpain cleavage pattern indicative of
      conformational alterations. In conclusion, tumor-associated OD mutants of p53 can
      be functionally competent to different degrees despite of being oligomerization
      defective.
CI  - Copyright 2000 Wiley-Liss, Inc.
FAU - Atz, J
AU  - Atz J
AD  - Department of Virology, University of Saarland Medical School, D-66421
      Homburg/Saar, Germany.
FAU - Wagner, P
AU  - Wagner P
FAU - Roemer, K
AU  - Roemer K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Antibodies)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Epitopes)
RN  - 0 (Repressor Proteins)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 3.4.22.- (Calpain)
SB  - IM
MH  - Antibodies/metabolism
MH  - Apoptosis/genetics
MH  - Calpain/metabolism
MH  - Centrifugation, Density Gradient
MH  - DNA-Binding Proteins/chemistry/genetics
MH  - Epitopes/genetics/immunology
MH  - Genes, Reporter/genetics
MH  - Humans
MH  - Mutation
MH  - *Protein Conformation
MH  - Repressor Proteins/genetics
MH  - Transcriptional Activation/genetics
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Protein p53/*chemistry/genetics
EDAT- 2000/02/02 09:00
MHDA- 2000/03/11 09:00
CRDT- 2000/02/02 09:00
PHST- 2000/02/02 09:00 [pubmed]
PHST- 2000/03/11 09:00 [medline]
PHST- 2000/02/02 09:00 [entrez]
AID - 10.1002/(SICI)1097-4644(20000315)76:4<572::AID-JCB6>3.0.CO;2-6 [pii]
AID - 10.1002/(sici)1097-4644(20000315)76:4<572::aid-jcb6>3.0.co;2-6 [doi]
PST - ppublish
SO  - J Cell Biochem. 2000 Jan;76(4):572-84. doi:
      10.1002/(sici)1097-4644(20000315)76:4<572::aid-jcb6>3.0.co;2-6.