Publication: Identification and characterization of genes responsive to apoptosis. Application of DNA chip technology and mRNA differential display
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Date
2000
Authors
Sun, Y.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Apoptosis (programmed cell death) is a
genetically programmed active cell death process for
maintaining homeostasis under physiological conditions
and for responding to various stimuli. Many human
diseases have been associated with either increased
apoptosis (such as AIDS and neurodegenerative
disorders) or decreased apoptosis (such as cancer and
autoimmune disorders). In an attempt to understand
apoptosis signaling pathway and genes associated with
apoptosis, we established two cell model systems on
which apoptosis is induced either by DNA damaging
agent, etoposide or by redox agent, 1,lO-phenanthroline
(OP). DNA chip profiling or mRNA differential display
(DD) was utilized to identify genes responsive to
apoptosis induced by these two agents. In etoposide
model with chip hybridization, we defined signaling
pathways that mediate apoptosis in p53 dependent
manner (through activation of p53 target genes such as
Waf-lIp21, PCNA, GPX, S100A2 and PTGF-S) as well
as in p53-independent manner (through activation of
ODC and TGF-S receptor, among others). In OP model
with DD screening, we cloned and characterized two
genes: glutathione synthetase, encoding an enzyme
involved in glutathione synthesis and Sensitive to
Apoptosis Gene (SAG), a novel evolutionarily conserved
gene encoding a zinc RING finger protein. Both genes
appear to protect cells from apoptosis induced by redox
agents. Further characterization of SAG revealed that it
is a growth essential gene in yeast and belongs to a
newly identified gene family that promotes protein
ubiquitination and degradation. Through this activity,
SAG regulates cell cycle progression and many other key
biological processes. Thus, SAG could be a valid drug
target for anti-cancer and anti-inflammation therapies.
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