ERK8 is a novel HuR kinase that regulates tumour suppressor PDCD4 through a miR-21 dependent mechanism
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Urszula Liwak-Muir1, Christine C. Dobson1, Thet Naing1, Quinlan Wylie1, Lucia Chehade1, Stephen D. Baird1, Pranesh K. Chakraborty2,3 and Martin Holcik1,2
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
Martin Holcik, email:
Keywords: tumour supressor, miRNA, kinase
Received: September 14, 2015 Accepted: November 16, 2015 Published: November 22, 2015
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 H2O2 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 H2O2 treatment. We show that phosphorylation of HuR by ERK8 prevents it from binding to PDCD4 mRNA and allows miR-21-mediated degradation of PDCD4.
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