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The integrated stress response and proteotoxicity in cancer therapy.

Abstract：

:A variety of different forms of cellular stress can cause protein misfolding and aggregation and proteotoxicity. The cytoprotective response to proteotoxicity is termed the integrated stress response and involves 4 distinct serine/threonine protein kinases that converge on the translation initiation factor eIF2α, resulting in phosphorylation at S51, cell cycle arrest, and a general inhibition of global protein synthesis. Phosphorylation of eIF2α also promotes translation of ATF4 and the expression of ATF4 target genes that ameliorate proteotoxic stress but can also promote apoptosis. This mini review provides a general overview of these mechanisms and discusses how the inter-tumor heterogeneity that involves them affects sensitivity and resistance to proteasome inhibitors, a new class of cancer therapeutics that promotes tumor cell killing via proteotoxic stress.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

McConkey DJ

doi

10.1016/j.bbrc.2016.11.047

subject

Has Abstract

pub_date

2017-01-15 00:00:00

pages

450-453

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(16)31902-7

journal_volume

482

pub_type

杂志文章,评审

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