Abstract
Eukaryotic cells, when exposed to stress, stop
protein translation and form cytoplasmic granules
called stress granules (SGs) containing mRNAs
and mRNA-binding proteins such as Ras-GAP SH3
domain-binding protein (G3BP) 1 and 2. Cells are
thought to survive stress by utilizing SGs as the
platform of RNA triage. Accordingly, in cancer
cells, SGs are proposed to cause resistance
against anti-cancer drugs. We initiated this study
to identify novel compounds that induce SGs.
We exposed human keratinocyte HaCaT cells to
various chemical compounds and immunostained
them with anti-G3BP antibody. We found that
the cells exposed to topoisomerase inhibitors,
teniposide and topotecan, form G3BP-containing
aggregates (GCAs). GCAs look like SGs, but are
formed more slowly and are not dissociated after
stress removal. GCA formation is not associated
with eIF2α phosphorylation, while in most cases SG
formation depends on it. More importantly, GCAs
do not contain representative components of SGs
or mRNAs. In sum, we have unexpectedly found a
novel cytoplasmic structure ｃontaining G3BP that
is distinct from SG.
