In response to accumulation of unfolded proteins in the endoplasmic reticulum (ER), a homoeostatic response, termed the unfolded protein response (UPR), is activated in all eukaryotic cells. The UPR involves only transcriptional regulation in yeast, and approx. 6% of all yeast genes, encoding not only proteins to augment the folding capacity in the ER, but also proteins working at various stages of secretion, are induced by ER stress [Travers, Patil, Wodicka, Lockhart, Weissman and Walter (2000) Cell (Cambridge, Mass.) 101, 249–258]. In the present study, we conducted microarray analysis of HeLa cells, although our analysis covered only a small fraction of the human genome. A great majority of human ER stress-inducible genes (approx. 1% of 1800 genes examined) were classified into two groups. One group consisted of genes encoding ER-resident molecular chaperones and folding enzymes, and these genes were directly regulated by the ER-membrane-bound transcription factor activating transcription factor (ATF) 6. The ER-membrane-bound protein kinase double-stranded RNA-activated protein kinase-like ER kinase (PERK)-mediated signalling pathway appeared to be responsible for induction of the remaining genes, which are not involved in secretion, but may be important after cellular recovery from ER stress. In higher eukaryotes, the PERK-mediated translational-attenuation system is known to operate in concert with the transcriptional-induction system. Thus we propose that mammalian cells have evolved a strategy to cope with ER stress different from that of yeast cells.
Skip Nav Destination
Article navigation
September 2002
- PDF Icon PDF LinkFront Matter
Research Article|
September 01 2002
Distinct roles of activating transcription factor 6 (ATF6) and double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase (PERK) in transcription during the mammalian unfolded protein response
Tetsuya OKADA;
Tetsuya OKADA
∗Graduate School of Biostudies, Kyoto University, 46-29 Yoshida-Shimoadachi, Sakyo-ku, Kyoto 606-8304, Japan,
Search for other works by this author on:
Hiderou YOSHIDA;
Hiderou YOSHIDA
∗Graduate School of Biostudies, Kyoto University, 46-29 Yoshida-Shimoadachi, Sakyo-ku, Kyoto 606-8304, Japan,
Search for other works by this author on:
Rieko AKAZAWA;
Rieko AKAZAWA
†HSP Research Institute, Kyoto Research Park, 17 Chudoji-minami, Shimogyo-ku, Kyoto 600-8813, Japan
Search for other works by this author on:
Manabu NEGISHI;
Manabu NEGISHI
∗Graduate School of Biostudies, Kyoto University, 46-29 Yoshida-Shimoadachi, Sakyo-ku, Kyoto 606-8304, Japan,
Search for other works by this author on:
Kazutoshi MORI
Kazutoshi MORI
1
∗Graduate School of Biostudies, Kyoto University, 46-29 Yoshida-Shimoadachi, Sakyo-ku, Kyoto 606-8304, Japan,
1To whom correspondence should be addressed (e-mail kazu.mori@bio.mbox.media.kyoto-u.ac.jp).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
March 07 2002
Revision Received:
May 09 2002
Accepted:
May 16 2002
Accepted Manuscript online:
May 16 2002
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2002
2002
Biochem J (2002) 366 (2): 585–594.
Article history
Received:
March 07 2002
Revision Received:
May 09 2002
Accepted:
May 16 2002
Accepted Manuscript online:
May 16 2002
Citation
Tetsuya OKADA, Hiderou YOSHIDA, Rieko AKAZAWA, Manabu NEGISHI, Kazutoshi MORI; Distinct roles of activating transcription factor 6 (ATF6) and double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase (PERK) in transcription during the mammalian unfolded protein response. Biochem J 1 September 2002; 366 (2): 585–594. doi: https://doi.org/10.1042/bj20020391
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.