Format

Send to

Choose Destination
Nucleic Acids Res. 2016 May 5;44(8):3695-712. doi: 10.1093/nar/gkw057. Epub 2016 Feb 3.

The downregulation of the RNA-binding protein Staufen2 in response to DNA damage promotes apoptosis.

Author information

1
Département de Biochimie et médecine moléculaire, Faculté de médecine, Université de Montréal, 2900 Edouard Montpetit Montréal, QC H3T 1J4, Canada.
2
Département de Médecine, Université de Montréal and Centre de Recherche, Hôpital Maisonneuve Rosemont, Montréal, Québec, H1T 2M4, Canada.
3
Département de Biochimie et médecine moléculaire, Faculté de médecine, Université de Montréal, 2900 Edouard Montpetit Montréal, QC H3T 1J4, Canada luc.desgroseillers@umontreal.ca.

Abstract

Staufen2 (Stau2) is an RNA-binding protein involved in cell fate decision by controlling several facets of mRNA processing including localization, splicing, translation and stability. Herein we report that exposure to DNA-damaging agents that generate replicative stress such as camptothecin (CPT), 5-fluoro-uracil (5FU) and ultraviolet radiation (UVC) causes downregulation of Stau2 in HCT116 colorectal cancer cells. In contrast, other agents such as doxorubicin and ionizing radiation had no effect on Stau2 expression. Consistently, Stau2 expression is regulated by the ataxia telangiectasia and Rad3-related (ATR) signaling pathway but not by the DNA-PK or ataxia telangiectasia mutated/checkpoint kinase 2 pathways. Stau2 downregulation is initiated at the level of transcription, independently of apoptosis induction. Promoter analysis identified a short 198 bp region which is necessary and sufficient for both basal and CPT-regulated Stau2 expression. The E2F1 transcription factor regulates Stau2 in untreated cells, an effect that is abolished by CPT treatment due to E2F1 displacement from the promoter. Strikingly, Stau2 downregulation enhances levels of DNA damage and promotes apoptosis in CPT-treated cells. Taken together our results suggest that Stau2 is an anti-apoptotic protein that could be involved in DNA replication and/or maintenance of genome integrity and that its expression is regulated by E2F1 via the ATR signaling pathway.

PMID:
26843428
PMCID:
PMC4856980
DOI:
10.1093/nar/gkw057
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center