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J. Biol. Chem., Vol. 277, Issue 10, 8273-8278, March 8, 2002
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From the Department of Neuroscience, Georgetown University Medical
Center, Washington, D. C. 20007
Caspase-3 is the major effector in apoptosis
triggered by various stimuli. Previous studies demonstrated a
significant increase in transcriptional activity of the caspase-3 gene
during neuronal apoptosis. Recent findings suggest that differential
expression of the caspase-3 gene may underlie the regulation of
apoptotic susceptibility during brain development and after acute
injury to the mature brain. We identified and cloned the rat caspase-3 gene promoter, determined its structure, and examined its regulation during a course of apoptosis in PC12 cells. Results demonstrate that
this promoter lacks a TATA-box and contains a cluster of Sp1 elements
and multiple transcription start sites. The first identified
transcription start site is located 87-bp upstream from the first
splicing site. A role of Sp1 elements in the regulation of caspase-3
promoter activity is demonstrated by the inhibition of Sp1 binding
using mithramycin A. Results of deletion analysis show that an
Ets-1-like element located between nucleotides The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AF427079.
Identification and Functional Analysis of the Rat Caspase-3 Gene
Promoter*
1646 and 1632
relative to the most extended transcription start site is necessary to
achieve sustained transcriptional activity. Homology analysis
revealed that the 5'-flanking region of the human caspase-3 gene
exhibits significant similarity to a regulatory region of the rat gene.
*
This work was supported by Grant NS38941 (to A. G. Y.)
from the NINDS, National Institutes of Health.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Neuroscience,
Georgetown University, Research Bldg., WP14, 3970 Reservoir Rd. NW,
Washington, D. C. 20007. Tel.: 202-687-1735; Fax: 202-687-0617; E-mail: yakovlev@giccs.georgetown.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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