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Selenoprotein W regulates epidermal growth factor receptor trafficking, expression, and activation (374.4)
Author(s) -
Hawkes Wayne,
Alkan Zeynep,
Duong Frank,
Rangan Priya
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.374.4
Subject(s) - epidermal growth factor receptor , microbiology and biotechnology , epidermal growth factor , protein kinase b , phosphorylation , mapk/erk pathway , chemistry , pi3k/akt/mtor pathway , erbb3 , growth factor receptor , cell growth , growth factor , receptor tyrosine kinase , biology , receptor , signal transduction , biochemistry
Epidermal growth factor (EGF) receptor (EGFR) is the founding member of the ErbB family of growth factor receptors that control growth, proliferation, differentiation, apoptosis, and cell migration. Selenoprotein W (SEPW1) is a highly conserved, ubiquitously expressed 9 kDa selenocysteine‐containing protein involved in cell cycle control. SEPW1 siRNA inhibited EGFR activation in RWPE‐1, MCF‐10A and MCF‐7 cells, while SEPW1 overexpression increased it. SEPW1 siRNA inhibited EGF‐induced activation of downstream pathways (MAPK, PI3K/Akt, JAK/STAT, and p53), and blocked EGF‐induced cell cycle entry. SEPW1 was associated with peripheral punctuate structures that partially co‐localized with EGFR. Ligand‐bound EGFR failed to traffic towards the nucleus in SEPW1‐depleted cells, indicating that SEPW1 has a role in EGFR trafficking. Consequently, the half‐life, expression, dimerization, and phosphorylation of EGFR were also decreased in SEPW1‐depleted cells. SEPW1 siRNA also inhibited hydrogen peroxide‐induced EGFR phosphorylation. However, SEPW1 siRNA inhibition of EGF‐stimulated EGFR phosphorylation was not decreased by N‐acetylcysteine or sodium orthovanadate, indicating SEPW1 regulation of EGFR does not involve reactive oxygen species or inhibition of protein tyrosine phosphatase. Glutathione peroxidase siRNA partially rescued EGF‐induced cell cycle entry in SEPW1‐depleted cells, showing the effect of SEPW1 depletion is not due to loss of antioxidant protection. Knowledge of the mechanisms underlying SEPW1 regulation of EGFR trafficking may be important to understanding the relationship between dietary selenium and cancer. Grant Funding Source : Supported by USDA CRIS Project 5306‐51530‐018‐00D