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ATM blocks tunicamycin‐induced endoplasmic reticulum stress
Author(s) -
He Long,
Kim Sun Ok,
Kwon Osong,
Jeong Sook Jung,
Kim Min Soo,
Lee Hee Gu,
Osada Hiroyuki,
Jung Mira,
Ahn Jong Seog,
Kim Bo Yeon
Publication year - 2009
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.02.002
Subject(s) - tunicamycin , endoplasmic reticulum , unfolded protein response , transfection , microbiology and biotechnology , chemistry , gene knockdown , chop , cancer research , biology , apoptosis , biochemistry , gene
Endoplasmic reticulum stress (ER‐stress) is associated with ataxia telangiectasia mutated (ATM) gene. We present here conclusive data showing that ATM blocks ER‐stress induced by tunicamycin or ionizing radiation (IR). X‐box protein‐1 (XBP‐1) splicing, GRP78 expression and caspase‐12 activation were increased by tunicamycin or IR in Atm‐deficient AT5BIVA fibroblasts. Activation of caspase‐12 and caspase‐3 by tunicamycin was significantly reduced in cells transfected with wild‐type Atm (AT5BIVA/wtATM). Atm knockdown by siRNA, however, noticeably elevated ER‐stress and chemosensitivity to tunicamycin. In summary, we present substantial data demonstrating that ATM blocks the ER stress signaling associated with cancer cell proliferation.