Stress-Induced Accumulation of HnRNP K into Stress Granules.

Abstract

Stress granules (SGs) are cytoplasmic aggregates to reprogram gene expression in response to cellular stimulus. Here, we show that while SGs are being assembled in response to clotrimazole, an antifungal medication heterogeneous nuclear ribonucleoprotein (hnRNP) K, an RNA-binding protein that mediates translational silencing of mRNAs, is rapidly accumulated in SGs in U-2OS osteosarcoma cells. Forced expression of hnRNP K induces resistance to clotrimazole-induced apoptosis. Erk/MAPK is transiently activated in response to clotrimazole, and pharmacological suppression of the Erk/MAPK pathway sensitizes the cells to apoptosis. Inhibition of the Erk/MAPK pathway promotes the assembly of SGs. These results suggest that dynamic cytoplasmic formation of SGs and hnRNP K relocation to SGs may be defensive mechanisms against clotrimazole–induced apoptosis in U-2OS osteosarcoma cells.