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Mol. Cell. Biol., Mar 1997, 1615-1625, Vol 17, No. 3
N Levy-Strumpf, LP Deiss, H Berissi and A Kimchi
A functional approach to gene cloning was applied to HeLa cells in an
attempt to isolate cDNA fragments which convey resistance to gamma
interferon (IFN-gamma)-induced programmed cell death. One of the rescued
cDNAs, described in this work, was a fragment of a novel gene, named DAP-5.
Analysis of a DAP-5 full-length cDNA clone revealed that it codes for a
97-kDa protein that is highly homologous to eukaryotic translation
initiation factor 4G (eIF4G, also known as p220). According to its deduced
amino acid sequence, this novel protein lacks the N- terminal region of
eIF4G responsible for association with the cap binding protein eIF4E. The
N-terminal part of DAP-5 has 39% identity and 63% similarity to the central
region of mammalian p220. Its C- terminal part is less homologous to the
corresponding region of p220, suggesting that it may possess unique
functional properties. The rescued DAP-5 cDNA fragment which conveyed
resistance to IFN-gamma- induced cell death was expressed from the vector
in the sense orientation. Intriguingly, it comprised part of the coding
region which corresponds to the less conserved C-terminal part of DAP-5 and
directed the synthesis of a 28-kDa miniprotein. The miniprotein exerted a
dual effect on HeLa cells. Low levels of expression protected the cells
from IFN-gamma-induced programmed cell death, while high levels of
expression were not compatible with continuous cell growth. The relevance
of DAP-5 protein to possible changes in a cell's translational machinery
during programmed cell death and growth arrest is discussed.
Copyright © 1997, American Society for Microbiology
DAP-5, a novel homolog of eukaryotic translation initiation factor 4G isolated as a putative modulator of gamma interferon-induced programmed cell death
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
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