A close connection between the PERK and IRE arms of the UPR and the transcriptional regulation of autophagy

• Published in: Biochemical and biophysical research communications Vol. 456; no. 1; pp. 305 - 311
• Main Authors: Deegan, Shane, Koryga, Izabela, Glynn, Sharon A., Gupta, Sanjeev, Gorman, Adrienne M., Samali, Afshin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02.01.2015
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Autophagy; Autophagy - genetics; DNA, Complementary - metabolism; eIF-2 Kinase - metabolism; Endoplasmic Reticulum Stress; Endoribonucleases - metabolism; ER stress; Gene Expression Profiling; Gene Expression Regulation; HCT116 Cells; Humans; IRE1; Membrane Proteins - metabolism; Oligonucleotide Array Sequence Analysis; PERK; Protein-Serine-Threonine Kinases - metabolism; Proteins - metabolism; Proto-Oncogene Proteins - metabolism; Sequestosome-1 Protein; Tumor Suppressor Proteins - metabolism; Unfolded Protein Response; Unfolded protein response (UPR); PBS; MOMP; XBP1; HSPA5; DTT; ER stress; PARP; PERK; ER; Autophagy; MEF; ATG; DDIT3; DNA; IRE1; PI; Tm; BFA; GAPDH; LC3; Unfolded protein response (UPR)
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2014.11.076

•Microarray of HCT116 cells.•Autophagy genes upregulated.•PERK and IRE1 important for regulation. Endoplasmic reticulum (ER) stress is known to lead to activation of both the unfolded protein response (UPR) and autophagy. Although regulatory connections have been identified between the UPR and autophagy, it is still unclear to what extent the UPR regulates the genes involved at the different stages of the autophagy pathway. Here, we carried out a microarray analysis of HCT116 cells subjected to ER stress and observed the transcriptional upregulation of a large cohort of autophagy-related genes. Of particular interest, we identified the transcriptional upregulation of the autophagy receptor genes SQSTM1/p62, NBR1 and BNIP3L/NIX in response to ER stress and show that the inhibition of the UPR transmembrane receptors, PERK and IRE1, abrogates this upregulation.