JAB1 participates in unfolded protein responses by association and dissociation with IRE1.
Recent papers have reported that neuronal death in patients with Alzheimer's disease, Parkinson's disease, and cerebral ischemia has its origin in the endoplasmic reticulum (ER). IRE1alpha is one of the ER stress transducers that detect the accumulation of unfolded proteins in the ER. IRE1alpha mediates two major cellular responses, which are the unfolded protein response (UPR), a defensive response, and apoptosis that leads to cell death. However, little is known about the regulatory mechanisms that select between the UPR and apoptosis. We identified Jun activation domain-binding protein-1 (JAB1) as a molecule that interacts with IRE1alpha using a yeast two-hybrid system. We demonstrated that JAB1 binds to IRE1alpha in the absence of stress, but that binding is decreased by ER stress inducers. Moreover, mutant JAB1 down-regulates the UPR signaling pathway through tight binding with IRE1alpha. These results suggested that JAB1 may act as a key molecule in selecting the UPR or cell death by association and dissociation with IRE1alpha.
Oono
Kayoko
K
Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Yoneda
Takunari
T
Manabe
Takayuki
T
Yamagishi
Satoru
S
Matsuda
Satoshi
S
Hitomi
Junichi
J
Miyata
Shingo
S
Mizuno
Tatsuyoshi
T
Imaizumi
Kazunori
K
Katayama
Taiichi
T
Tohyama
Masaya
M
D000906:Antibodies / Q000737:chemistry; D015153:Blotting, Western; D000075686:COP9 Signalosome Complex; D016923:Cell Death / Q000502:physiology; D002460:Cell Line; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000502:physiology; D004722:Endoribonucleases; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D009154:Mutation / Q000235:genetics / Q000502:physiology; D009710:Nucleotide Mapping; D010447:Peptide Hydrolases; D011233:Precipitin Tests; D017510:Protein Folding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D000906:Antibodies; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D014157:Transcription Factors; C403982:ERN2 protein, human; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex