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Elucidation for modulation of death receptor (DR) 5 to strengthen apoptotic signals in cancer cells

Authors
  • Min, Kyoung-jin
  • Woo, Seon Min
  • Shahriyar, Sk Abrar
  • Kwon, Taeg Kyu
Type
Published Article
Journal
Archives of Pharmacal Research
Publisher
Springer-Verlag
Publication Date
Jan 10, 2019
Volume
42
Issue
1
Pages
88–100
Identifiers
DOI: 10.1007/s12272-018-01103-y
Source
Springer Nature
Keywords
License
Green

Abstract

The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis via death receptor (DR) 4 or DR5 preferentially in cancer cells, and not in normal cells with relatively high decoy receptor expression. However, multiple mechanisms in cancer cells induce resistance to DRs-mediated apoptosis. Therefore, understanding of molecular mechanisms for resistance to DRs-mediated apoptosis can find the strategy to increase sensitivity. Although multiple proteins are involved in resistance to DRs-mediated apoptosis, we focus on modulation of DR5 to overcome resistance. Here, we discuss regulation of DR5 expression or activation by epigenetic modification, transcription factor at the transcriptional levels, micro RNA and RNA-binding proteins at the post-transcriptional levels, and ubiquitination and glycosylation at the post-translational levels. In addition, we also mention about relationship between localization of DR5 and death signaling activation. The purpose of this review is to help understand relationship between regulatory mechanisms of DR5 and resistance to TRAIL or DRs-targeted agonist monoclonal antibodies, and to develop innovative anti-cancer therapies through regulation of DR5 signaling.

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