Cross-Species Pathway Meta-Analysis of Gene Expression Data Associated with the Unfolded Protein Response

In eukaryotic cells, the endoplasmic reticulum (ER) is a major organelle for oxygen and nutrient sensing as cells adapt to their microenvironment.  Surface and secreted proteins are synthesized in the ER where proper protein folding is a necessary step.  Controlling the quality of protein products exported from the ER is critical to ensuring normal cellular function.  Changes in the ER interfere with proper folding of proteins causing an accumulation of unfolded proteins that can trigger the unfolded protein response (UPR).  The UPR regulates transcription and translation of genes in an attempt to re-establish homeostasis and restore ER functions.  If homeostasis of the ER cannot be re-established, sustained UPR activation can trigger apoptotic pathways activated to destroy the damaged cell in order to protect the organism.  Chronic ER stress, that initiates UPR, is increasingly being recognized as a factor in many diseases such as diabetes, neurodegenerative disorders and cancer. Using NCBI Geo Datasets and pathway analyses, we set out to determine the relationship of genes and common pathways involved in UPR for multiple species.  Pathways common across species are primarily associated with signal transduction, cellular communication and protein degradation.  Two of the common genes in expression data sets are DNA damage inducible transcript 3 (DDIT3) and activating transcription factors (ATF).  Both genes have been previously associated with UPR.  Additionally, a large number of transcription factor genes appear to be associated with UPR.  Cross-species analysis of gene expression data sets will allow us to identify novel genes associated with UPR.