Human keratinocyte HaCaT cells form aggregates containing Ras-GAP SH3 domain-binding proteins in the cytoplasm in response to a low dose of teniposide Human keratinocyte HaCaT cells form aggregates containing Ras-GAP SH3 domain-binding proteins in the cytoplasm in response to a low dose of teniposide
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Eukaryotic cells, when exposed to stress, stopprotein translation and form cytoplasmic granulescalled stress granules (SGs) containing mRNAsand mRNA-binding proteins such as Ras-GAP SH3domain-binding protein (G3BP) 1 and 2. Cells arethought to survive stress by utilizing SGs as theplatform of RNA triage. Accordingly, in cancercells, SGs are proposed to cause resistanceagainst anti-cancer drugs. We initiated this studyto identify novel compounds that induce SGs.We exposed human keratinocyte HaCaT cells tovarious chemical compounds and immunostainedthem with anti-G3BP antibody. We found thatthe cells exposed to topoisomerase inhibitors,teniposide and topotecan, form G3BP-containingaggregates (GCAs). GCAs look like SGs, but areformed more slowly and are not dissociated afterstress removal. GCA formation is not associatedwith eIF2α phosphorylation, while in most cases SGformation depends on it. More importantly, GCAsdo not contain representative components of SGsor mRNAs. In sum, we have unexpectedly found anovel cytoplasmic structure ｃontaining G3BP thatis distinct from SG.
- Journal of Medical and Dental Sciences
Journal of Medical and Dental Sciences 66(2), 23-30, 2019
Tokyo Medical and Dental University