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

Shane Deegan; Izabela Koryga; Sharon A Glynn; Sanjeev Gupta; Adrienne M Gorman; Afshin Samali

doi:10.1016/j.bbrc.2014.11.076

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

Biochem Biophys Res Commun. 2015 Jan 2;456(1):305-11. doi: 10.1016/j.bbrc.2014.11.076. Epub 2014 Dec 2.

Authors

Shane Deegan¹, Izabela Koryga¹, Sharon A Glynn², Sanjeev Gupta³, Adrienne M Gorman¹, Afshin Samali⁴

Affiliations

¹ Apoptosis Research Centre, National University of Ireland Galway, Ireland; School of Natural Sciences, National University of Ireland Galway, Ireland.
² Apoptosis Research Centre, National University of Ireland Galway, Ireland; Prostate Cancer Institute, National University of Ireland Galway, Ireland.
³ Apoptosis Research Centre, National University of Ireland Galway, Ireland; School of Medicine, National University of Ireland Galway, Ireland.
⁴ 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.

PMID: 25475719
DOI: 10.1016/j.bbrc.2014.11.076

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.

Keywords: Autophagy; ER stress; IRE1; PERK; Unfolded protein response (UPR).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / metabolism
Autophagy / genetics
DNA, Complementary / metabolism
Endoplasmic Reticulum Stress*
Endoribonucleases / metabolism*
Gene Expression Profiling
Gene Expression Regulation*
HCT116 Cells
Humans
Intracellular Signaling Peptides and Proteins
Membrane Proteins / metabolism
Oligonucleotide Array Sequence Analysis
Protein Serine-Threonine Kinases / metabolism*
Proteins / metabolism
Proto-Oncogene Proteins / metabolism
Sequestosome-1 Protein
Tumor Suppressor Proteins / metabolism
Unfolded Protein Response*
eIF-2 Kinase / metabolism*

Substances

Adaptor Proteins, Signal Transducing
BNIP3L protein, human
DNA, Complementary
Intracellular Signaling Peptides and Proteins
Membrane Proteins
NBR1 protein, human
Proteins
Proto-Oncogene Proteins
SQSTM1 protein, human
Sequestosome-1 Protein
Tumor Suppressor Proteins
EIF2AK3 protein, human
ERN1 protein, human
Protein Serine-Threonine Kinases
eIF-2 Kinase
Endoribonucleases