Fig. 1.—

Pathway of the 90-kilodalton heat-shock protein (Hsp90) cellular stress response. Hsp90 expression increases in response to environmental stress, which perturbs protein form and function (protein homeostasis), including proteins involved in genomic DNA repair (e.g., DNA Pol-η), transcriptional activity (PPARα/β), chromosome integrity, and epigenetic regulation (e.g., histone acetyltransferase, SmyD). Hsp90, along with the cochaperone Shutdown (Shu) is also necessary for loading of piwi-interacting RNAs (piRNAs) onto the PIWI protein complex. The PIWI/piRNA pathway can silence transposable elements (TEs) transcriptionally (left), through histone methylation (Me) or other modifications to histones (H), or post-transcriptionally (right), through RNA-interference-mediated targeting of TE transposase RNAs. Genomic DNA (gray), TE DNA/RNA (red), and piRNA (purple) are also shown.