title: A close connection between the PERK and IRE arms of the UPR and the transcriptional regulation of autophagy.
abstract: 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.
authors.affiliation: Apoptosis Research Centre, National University of Ireland Galway, Ireland; School of Natural Sciences, National University of Ireland Galway, Ireland.
authors.forename: Shane
authors.initials: S
authors.lastname: Deegan
authors.affiliation: Apoptosis Research Centre, National University of Ireland Galway, Ireland; School of Natural Sciences, National University of Ireland Galway, Ireland.
authors.forename: Izabela
authors.initials: I
authors.lastname: Koryga
authors.affiliation: Apoptosis Research Centre, National University of Ireland Galway, Ireland; Prostate Cancer Institute, National University of Ireland Galway, Ireland.
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Glynn
authors.affiliation: Apoptosis Research Centre, National University of Ireland Galway, Ireland; School of Medicine, National University of Ireland Galway, Ireland.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Apoptosis Research Centre, National University of Ireland Galway, Ireland; School of Natural Sciences, National University of Ireland Galway, Ireland.
authors.forename: Adrienne M
authors.initials: AM
authors.lastname: Gorman
authors.affiliation: Apoptosis Research Centre, National University of Ireland Galway, Ireland; School of Natural Sciences, National University of Ireland Galway, Ireland. Electronic address: afshin.samali@nuigalway.ie.
authors.forename: Afshin
authors.initials: A
authors.lastname: Samali
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D001343:Autophagy / Q000235:genetics; D018076:DNA, Complementary / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D004722:Endoribonucleases / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D045325:HCT116 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D000071456:Sequestosome-1 Protein; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D056811:Unfolded Protein Response; D019892:eIF-2 Kinase / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C116838:BNIP3L protein, human; D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C549756:NBR1 protein, human; D011506:Proteins; D011518:Proto-Oncogene Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D025521:Tumor Suppressor Proteins; C460640:EIF2AK3 protein, human; C528229:ERN1 protein, human; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase; D004722:Endoribonucleases
keywords: Autophagy; ER stress; IRE1; PERK; Unfolded protein response (UPR)