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PMID:18281285

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Citation

Luo, D, He, Y, Zhang, H, Yu, L, Chen, H, Xu, Z, Tang, S, Urano, F and Min, W (2008) AIP1 is critical in transducing IRE1-mediated endoplasmic reticulum stress response. J. Biol. Chem. 283:11905-12

Abstract

We have previously shown that ASK1-interacting protein 1 (AIP1) transduces tumor necrosis factor-induced ASK1-JNK signaling. Because endoplasmic reticulum (ER) stress activates ASK1-JNK signaling cascade, we investigated the role of AIP1 in ER stress-induced signaling. We created AIP1-deficient mice (AIP1-KO) from which mouse embryonic fibroblasts and vascular endothelial cells were isolated. AIP1-KO cells show dramatic reductions in ER stress-induced, but not oxidative stress-induced, ASK1-JNK activation and cell apoptosis. The ER stress-induced IRE1-JNK/XBP-1 axis, but not the PERK-CHOP1 axis, is blunted in AIP1-KO cells. ER stress induced formation of an AIP1-IRE1 complex, and the PH domain of AIP1 is critical for the IRE1 interaction. Furthermore, reconstitution of AIP1-KO cells with AIP1 wild type, not an AIP1 mutant with a deletion of the PH domain (AIP1-DeltaPH), restores ER stress-induced IRE1-JNK/XBP-1 signaling. AIP1-IRE1 association facilitates IRE1 dimerization, a critical step for activation of IRE1 signaling. More importantly, AIP1-KO mice show impaired ER stress-induced IRE1-dependent signaling in vivo. We conclude that AIP1 is essential for transducing the IRE1-mediated ER stress response.

Links

PubMed PMC2335342 Online version:10.1074/jbc.M710557200

Keywords

Animals; Apoptosis; Cattle; DNA-Binding Proteins; Dimerization; Endoplasmic Reticulum/enzymology; Endoplasmic Reticulum/pathology; Endothelial Cells/cytology; Endothelial Cells/enzymology; Enzyme Activation; Humans; JNK Mitogen-Activated Protein Kinases/metabolism; MAP Kinase Kinase Kinase 5/metabolism; Membrane Proteins/metabolism; Mice; Mice, Knockout; Protein Binding; Protein Structure, Tertiary; Protein-Serine-Threonine Kinases/metabolism; Signal Transduction; Transcription Factors; ras GTPase-Activating Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:TRAF2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q3UHC7,UniProtKB:Q9EQY0

F

  • occurs_in:(CL:2000016)

Seeded From UniProt

complete

MOUSE:TRAF2

enables

GO:0044877: protein-containing complex binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_in:(CL:2000016)
  • has_input:(UniProtKB:Q3UHC7)
  • has_input:(UniProtKB:Q9EQY0)
  • has_input:(GO:1990597)

Seeded From UniProt

complete

MOUSE:DAB2P

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P39429,UniProtKB:Q9EQY0

F

  • occurs_in:(CL:2000016)

Seeded From UniProt

complete

MOUSE:DAB2P

part_of

GO:1990597: AIP1-IRE1 complex

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9EQY0

C

Seeded From UniProt

complete

MOUSE:DAB2P

enables

GO:0019901: protein kinase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9EQY0

F

Seeded From UniProt

complete

MOUSE:DAB2P

involved_in

GO:0070059: intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:DAB2P

involved_in

GO:0043507: positive regulation of JUN kinase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:DAB2P

involved_in

GO:0071356: cellular response to tumor necrosis factor

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:DAB2P

part_of

GO:1990597: AIP1-IRE1 complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:DAB2P

enables

GO:0019901: protein kinase binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(PR:000007185)

Seeded From UniProt

complete

HUMAN:DAB2P

involved_in

GO:0031334: positive regulation of protein-containing complex assembly

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(UniProtKB:Q76MJ5)
  • has_input:(UniProtKB:O75460)

Seeded From UniProt

complete

HUMAN:DAB2P

involved_in

GO:0070059: intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q3UHC7

P

Seeded From UniProt

complete

MOUSE:ERN1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q3UHC7

F

Seeded From UniProt

complete

MOUSE:ERN1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P39429,UniProtKB:Q3UHC7

F

  • occurs_in:(CL:2000016)

Seeded From UniProt

complete

MOUSE:ERN1

part_of

GO:1990597: AIP1-IRE1 complex

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q3UHC7

C

Seeded From UniProt

complete

MOUSE:ERN1

part_of

GO:1990597: AIP1-IRE1 complex

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q3UHC7

C

exists_during:(GO:0034976)

Seeded From UniProt

complete


See also

References

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