IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA.
摘要：
The unfolded protein response (UPR), caused by stress, matches the folding capacity of endoplasmic reticulum (ER) to the load of client proteins in the organelle. In yeast, processing of HAC1 mRNA by activated Ire1 leads to synthesis of the transcription factor Hac1 and activation of the UPR. The responses to activated IRE1 in metazoans are less well understood. Here we demonstrate that mutations in either ire-1 or the transcription-factor-encoding xbp-1 gene abolished the UPR in Caenorhabditis elegans. Mammalian XBP-1 is essential for immunoglobulin secretion and development of plasma cells, and high levels of XBP-1 messenger RNA are found in specialized secretory cells. Activation of the UPR causes IRE1-dependent splicing of a small intron from the XBP-1 mRNA both in C. elegans and mice. The protein encoded by the processed murine XBP-1 mRNA accumulated during the UPR, whereas the protein encoded by unprocessed mRNA did not. Purified mouse IRE1 accurately cleaved XBP-1 mRNA in vitro, indicating that XBP-1 mRNA is a direct target of IRE1 endonucleolytic activity. Our findings suggest that physiological ER load regulates a developmental decision in higher eukaryotes.
展开
关键词：
Cell Line Endoplasmic Reticulum Fibroblasts Stem Cells Animals Mice Caenorhabditis elegans Protein-Serine-Threonine Kinases DNA-Binding Proteins Caenorhabditis elegans Proteins
DOI：
10.1038/415092a
被引量：
年份：
2002
Taylor & Francis
BMJ
Nature
Nature
(全网免费下载)
Semantic Scholar
查看更多
万方医学
dx.doi.org
Europe PMC
Cell Press
NCBI
Oxford Univ Press
NCBI
adsabs.harvard.edu
dialnet.unirioja.es
EureKaMag.com
(全网免费下载)
ResearchGate
(全网免费下载)
ProQuest
ResearchGate
EBSCO
EBSCO
ron.medschl.cam.ac.uk
(全网免费下载)
mysciencework.com
science-open.com
www.socolar.com
scienceopen.com
cghjournal.org
ron.cimr.cam.ac.uk
(全网免费下载)
onAcademic
jlr.org
ajpgi.physiology.org
jcs.biologists.org
jcb.rupress.org
plantcell.org
molbiolcell.org
addgene.org
haematologica.org
wormbook.org
atvb.ahajournals.org
mcponline.org
mendeley.com
mct.aacrjournals.org
f1000.com
pubfacts.com
emboj.embopress.org
perspectivesinmedicine.cshlp.org
g3journal.org
ideas.repec.org
readcube.com
jacionline.org
Nature
(全网免费下载)
ResearchGate
(全网免费下载)
EureKaMag.com
(全网免费下载)
ron.cimr.cam.ac.uk
(全网免费下载)
ron.medschl.cam.ac.uk
(全网免费下载)
通过文献互助平台发起求助，成功后即可免费获取论文全文。
相似文献
参考文献
引证文献
来源期刊
引用走势
站内活动
辅助模式
引用
文献可以批量引用啦~
欢迎点我试用！
