Type

Other / n/a

Authors

Jochen HM 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 proteins endoplasmic reticulum er stress microrna sh sy5y cells cortical neurons cell death transcription factor bcl 2 family

Endoplasmic reticulum stress-mediated upregulation of miR-29a enhances sensitivity to neuronal apoptosis. (2016)

Abstract Disturbance of homeostasis within the endoplasmic reticulum (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. Previously the Bcl-2 homology domain 3-Only Protein Puma was identified as a mediator of ER stress-induced apoptosis in neurons. In the search of alternative contributors to ER stress-induced apoptosis, a downregulation of the anti-apoptotic Bcl-2 family protein Mcl-1 was noted 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'-untranslated region 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). The current data demonstrate that the ATF4-mediated upregulation of miR-29a enhances the sensitivity of neurons to ER stress-induced apoptosis.
Collections Ireland -> Royal College of Surgeons in Ireland -> Department of Molecular and Cellular Therapeutics
Ireland -> Royal College of Surgeons in Ireland -> Physiology and Medical Physics Articles
Ireland -> Royal College of Surgeons in Ireland -> Cancer Genetics Articles
Ireland -> Royal College of Surgeons in Ireland -> Molecular and Cellular Therapeutics Articles
Ireland -> Royal College of Surgeons in Ireland -> Department of Cancer Genetics
Ireland -> Royal College of Surgeons in Ireland -> Department of Physiology and Medical Physics

Full list of authors on original publication

Jochen HM 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