Downregulation of miR-17-92 Cluster by PERK Fine-Tunes Unfolded Protein Response Mediated Apoptosis.

An important event in the unfolded protein response (UPR) is activation of the endoplasmic reticulum (ER) kinase PERK. The PERK signalling branch initially mediates a prosurvival response, which progresses to a proapoptotic response upon prolonged ER stress. However, the molecular mechanisms of PERK-mediated cell death are not well understood.

Disruption of microRNA biogenesis confers resistance to ER stress-induced cell death upstream of the mitochondrion.

Global downregulation of microRNAs (miRNAs) is a common feature of human tumors and has been shown to enhance cancer progression. Several components of the miRNA biogenesis machinery (XPO5, DICER and TRBP) have been shown to act as haploinsufficient tumor suppressors. How the deregulation of miRNA biogenesis promotes tumor development is not clearly understood.

Assays for detecting the unfolded protein response.

The endoplasmic reticulum (ER) is the site for folding of membrane and secreted proteins in the cell. Physiological or pathological processes that disturb protein folding in the ER cause ER stress and activate a set of signaling pathways termed the unfolded protein response (UPR). The UPR leads to transcriptional activation of genes encoding ER-resident chaperones, oxidoreductases, and ER-associated degradation (ERAD) components.