PMID- 10564271
OWN - NLM
STAT- MEDLINE
DCOM- 19991209
LR  - 20181113
IS  - 1059-1524 (Print)
IS  - 1059-1524 (Linking)
VI  - 10
IP  - 11
DP  - 1999 Nov
TI  - Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and
      activated by proteolysis in response to endoplasmic reticulum stress.
PG  - 3787-99
AB  - The unfolded protein response (UPR) controls the levels of molecular chaperones
      and enzymes involved in protein folding in the endoplasmic reticulum (ER). We
      recently isolated ATF6 as a candidate for mammalian UPR-specific transcription
      factor. We report here that ATF6 constitutively expressed as a 90-kDa protein
      (p90ATF6) is directly converted to a 50-kDa protein (p50ATF6) in ER-stressed
      cells. Furthermore, we showed that the most important consequence of this
      conversion was altered subcellular localization; p90ATF6 is embedded in the ER,
      whereas p50ATF6 is a nuclear protein. p90ATF6 is a type II transmembrane
      glycoprotein with a hydrophobic stretch in the middle of the molecule. Thus, the 
      N-terminal half containing a basic leucine zipper motif is oriented facing the
      cytoplasm. Full-length ATF6 as well as its C-terminal deletion mutant carrying
      the transmembrane domain is localized in the ER when transfected. In contrast,
      mutant ATF6 representing the cytoplasmic region translocates into the nucleus and
      activates transcription of the endogenous GRP78/BiP gene. We propose that ER
      stress-induced proteolysis of membrane-bound p90ATF6 releases soluble p50ATF6,
      leading to induced transcription in the nucleus. Unlike yeast UPR, mammalian UPR 
      appears to use a system similar to that reported for cholesterol homeostasis.
FAU - Haze, K
AU  - Haze K
AD  - HSP Research Institute, Kyoto Research Park, Shimogyo-ku, Kyoto 600-8813, Japan.
FAU - Yoshida, H
AU  - Yoshida H
FAU - Yanagi, H
AU  - Yanagi H
FAU - Yura, T
AU  - Yura T
FAU - Mori, K
AU  - Mori K
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Mol Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
RN  - 0 (ATF6 protein, human)
RN  - 0 (Activating Transcription Factor 6)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Transcription Factors)
RN  - 11089-65-9 (Tunicamycin)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 3.4.- (Endopeptidases)
SB  - IM
MH  - Activating Transcription Factor 6
MH  - DNA-Binding Proteins/*metabolism
MH  - Endopeptidases/metabolism
MH  - Endoplasmic Reticulum/genetics/*metabolism
MH  - Fluorescent Antibody Technique
MH  - Glycosylation
MH  - HeLa Cells
MH  - Humans
MH  - Membrane Glycoproteins/*metabolism
MH  - Molecular Weight
MH  - Nuclear Proteins/metabolism
MH  - Protein Folding
MH  - Protein Processing, Post-Translational
MH  - Solubility
MH  - Thapsigargin/pharmacology
MH  - Transcription Factors/*metabolism
MH  - Transfection
MH  - Tunicamycin/pharmacology
PMC - PMC25679
EDAT- 1999/11/17 00:00
MHDA- 1999/11/17 00:01
CRDT- 1999/11/17 00:00
PHST- 1999/11/17 00:00 [pubmed]
PHST- 1999/11/17 00:01 [medline]
PHST- 1999/11/17 00:00 [entrez]
AID - 10.1091/mbc.10.11.3787 [doi]
PST - ppublish
SO  - Mol Biol Cell. 1999 Nov;10(11):3787-99. doi: 10.1091/mbc.10.11.3787.