Type

Journal Article

Authors

Jochen H M Prehn
Caoimhín G Concannon
Raymond L Stallings
Isabella Bray
Stefan Haunsberger
Ross Gallagher
Simone Poeschel
Liam P Tuffy
Franziska Walter
Katie Nolan

Subjects

Biochemistry

Topics
bcl 2 family 1 protein gene silencing er stress sh sy5y cells cell death stress response transcription factor

ER Stress-Mediated Upregulation of miR-29a Enhances Sensitivity to Neuronal Apoptosis. (2015)

Abstract Disturbance of homeostasis within the ER lumen leads to the accumulation of unfolded and misfolded proteins. This results in the activation of an evolutionary conserved stress response termed ER stress that, if unresolved, induces apoptosis. We previously identified the Bcl-2 homology domain 3 (BH3)-Only Protein Puma as a mediator of ER stress-induced apoptosis in neurons. In the search of alternative contributors to ER stress-induced apoptosis, we noted a downregulation of the anti-apoptotic Bcl-2 family protein Mcl-1 during ER stress in both mouse cortical neurons and human SH-SY5Y neuroblastoma cells. Downregulation of Mcl-1 was associated with an upregulation of microRNA-29a (miR-29a) expression, and subsequent experiments showed that miR-29a targeted the 3' UTR of the anti-apoptotic Bcl-2 family protein, Mcl-1. Inhibition of miR-29a expression using sequence specific antagomirs or the overexpression of Mcl-1 decreased cell death following tunicamycin treatment, while gene silencing of Mcl-1 increased cell death. miR-29a did not alter the signalling branches of the ER stress response, rather its expression was controlled by the ER stress-induced transcription factor activating-transcription-factor-4 (ATF4). Our data demonstrate that the ATF4-mediated upregulation of miR-29a enhances the sensitivity of neurons to ER stress-induced apoptosis. This article is protected by copyright. All rights reserved.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Jochen H M Prehn, Caoimhín G Concannon, Raymond L Stallings, Isabella Bray, Stefan Haunsberger, Ross Gallagher, Simone Poeschel, Liam P Tuffy, Franziska Walter, Katie Nolan

Experts in our system

1
Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
 
2
Caoimhín G Concannon
Royal College of Surgeons in Ireland
Total Publications: 46
 
3
Raymond L Stallings
Royal College of Surgeons in Ireland
Total Publications: 59
 
4
Isabella Bray
Royal College of Surgeons in Ireland
Total Publications: 35
 
5
Liam P Tuffy
Royal College of Surgeons in Ireland
Total Publications: 13
 
6
Franziska Walter
Royal College of Surgeons in Ireland
Total Publications: 5
 
7
Katie Nolan
Royal College of Surgeons in Ireland
Total Publications: 5