Oncotarget

Research Papers:

ERK8 is a novel HuR kinase that regulates tumour suppressor PDCD4 through a miR-21 dependent mechanism

Urszula Liwak-Muir, Christine C. Dobson, Thet Naing, Quinlan Wylie, Lucia Chehade, Stephen D. Baird, Pranesh K. Chakraborty and Martin Holcik _

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Oncotarget. 2016; 7:1439-1450. https://doi.org/10.18632/oncotarget.6363

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Abstract

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

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 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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