PMID- 10329733
OWN - NLM
STAT- MEDLINE
DCOM- 19990709
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 21
DP  - 1999 May 21
TI  - p53 suppresses the activation of the Bcl-2 promoter by the Brn-3a POU family
      transcription factor.
PG  - 15237-44
AB  - The Brn-3a POU family transcription factor has been shown to strongly activate
      expression of the Bcl-2 proto-oncogene and thereby protect neuronal cells from
      programmed cell death (apoptosis). This activation of the Bcl-2 promoter by
      Brn-3a is strongly inhibited by the p53 anti-oncogene protein. This inhibitory
      effect of p53 on Brn-3a-mediated transactivation is observed with nonoverlapping 
      gene fragments containing either the Bcl-2 p1 or p2 promoters but is not observed
      with other Brn-3a-activated promoters such as in the gene encoding
      alpha-internexin or with an isolated Brn-3a binding site from the Bcl-2 promoter 
      linked to a heterologous promoter. In contrast, p53 mutants, which are incapable 
      of binding to DNA, do not affect Brn-3a-mediated activation of the Bcl-2 p1 and
      p2 promoters. Moreover, Brn-3a and p53 have been shown to bind to adjacent sites 
      in the p2 promoter and to directly interact with one another, both in vitro and
      in vivo, with this interaction being mediated by the POU domain of Brn-3a and the
      DNA binding domain of p53. The significance of these effects is discussed in
      terms of the antagonistic effects of Bcl-2 and p53 on the rate of apoptosis and
      the overexpression of Brn-3a in specific tumor cell types.
FAU - Budhram-Mahadeo, V
AU  - Budhram-Mahadeo V
AD  - Department of Molecular Pathology, Windeyer Institute of Medical Sciences,
      University College London Medical School, Windeyer Building, 46 Cleveland Street,
      London W1P 6DB, United Kingdom.
FAU - Morris, P J
AU  - Morris PJ
FAU - Smith, M D
AU  - Smith MD
FAU - Midgley, C A
AU  - Midgley CA
FAU - Boxer, L M
AU  - Boxer LM
FAU - Latchman, D S
AU  - Latchman DS
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 (DNA-Binding Proteins)
RN  - 0 (Transcription Factor Brn-3)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Cells, Cultured
MH  - DNA-Binding Proteins/*physiology
MH  - Genes, bcl-2/*genetics/*physiology
MH  - Genes, p53/*physiology
MH  - Promoter Regions, Genetic
MH  - Transcription Factor Brn-3
MH  - Transcription Factors/*physiology
EDAT- 1999/05/18 00:00
MHDA- 1999/05/18 00:01
CRDT- 1999/05/18 00:00
PHST- 1999/05/18 00:00 [pubmed]
PHST- 1999/05/18 00:01 [medline]
PHST- 1999/05/18 00:00 [entrez]
AID - 10.1074/jbc.274.21.15237 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 May 21;274(21):15237-44. doi: 10.1074/jbc.274.21.15237.