2. Academic Validation
  3. ERK8 is a novel HuR kinase that regulates tumour suppressor PDCD4 through a miR-21 dependent mechanism

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

  • Oncotarget. 2016 Jan 12;7(2):1439-50. doi: 10.18632/oncotarget.6363.
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,  Martin Holcik 1 2
Affiliations

Affiliations

  • 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.
PMID: 26595526 DOI: 10.18632/oncotarget.6363
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.

Keywords

kinase; miRNA; tumour supressor.

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