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ERK8 is a novel HuR kinase that regulates tumour suppressor PDCD4 through a miR-21 dependent mechanism
- Source :
- Oncotarget
- Publication Year :
- 2015
- Publisher :
- Impact Journals LLC, 2015.
-
Abstract
- // Urszula Liwak-Muir 1 , Christine C. Dobson 1 , Thet Naing 1 , Quinlan Wylie 1 , Lucia Chehade 1 , Stephen D. Baird 1 , Pranesh K. Chakraborty 2,3 and Martin Holcik 1,2 1 Molecular Biomedicine Program, Children’s Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada 2 Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada 3 Newborn Screening Ontario, Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada Correspondence to: Martin Holcik, email: // Keywords : tumour supressor, miRNA, kinase Received : September 14, 2015 Accepted : November 16, 2015 Published : November 22, 2015 Abstract Programmed cell death 4 (PDCD4) is a tumour suppressor implicated in cancer development and progression and was recently identified as a repressor of cap-independent translation of specific genes involved in the regulation of apoptosis. We show that the RNA-binding protein HuR binds to the PDCD4 3’UTR to protect it from miR-21-induced silencing. However, following H 2 O 2 treatment, PDCD4 mRNA is degraded via miR-21 binding. Importantly, we identify HuR as a novel substrate of the ERK8 kinase pathway in response to H 2 O 2 treatment. We show that phosphorylation of HuR by ERK8 prevents it from binding to PDCD4 mRNA and allows miR-21-mediated degradation of PDCD4.
- Subjects :
- 0301 basic medicine
Time Factors
kinase
RNA Stability
Repressor
Uterine Cervical Neoplasms
RNA-binding protein
Biology
Transfection
ELAV-Like Protein 1
03 medical and health sciences
RNA interference
microRNA
Gene silencing
Humans
Gene Silencing
RNA, Messenger
Phosphorylation
Extracellular Signal-Regulated MAP Kinases
3' Untranslated Regions
miRNA
Binding Sites
Three prime untranslated region
Kinase
RNA-Binding Proteins
Hydrogen Peroxide
3. Good health
Enzyme Activation
Gene Expression Regulation, Neoplastic
MicroRNAs
030104 developmental biology
Oncology
Cancer research
tumour supressor
Female
RNA Interference
Signal transduction
Apoptosis Regulatory Proteins
Research Paper
HeLa Cells
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 19492553
- Volume :
- 7
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....6605be4ee2a67ba1cccf79cfd097e16d