title: BBF2H7, a novel transmembrane bZIP transcription factor, is a new type of endoplasmic reticulum stress transducer.
abstract: Endoplasmic reticulum (ER) stress transducers IRE1 (inositol requiring 1), PERK (PKR-like endoplasmic reticulum kinase), and ATF6 (activating transcription factor 6) are well known to transduce signals from the ER to the cytoplasm and nucleus when unfolded proteins accumulate in the ER. Recently, we identified OASIS (old astrocyte specifically induced substance) as a novel ER stress transducer expressed in astrocytes. We report here that BBF2H7 (BBF2 human homolog on chromosome 7), an ER-resident transmembrane protein with the bZIP domain in the cytoplasmic portion and structurally homologous to OASIS, is cleaved at the membrane in response to ER stress. The cleaved fragments of BBF2H7 translocate into the nucleus and can bind directly to cyclic AMP-responsive element sites to activate transcription of target genes. Interestingly, although BBF2H7 protein is not expressed under normal conditions, it is markedly induced at the translational level during ER stress, suggesting that BBF2H7 might contribute to only the late phase of unfolded protein response signaling. In a mouse model of focal brain ischemia, BBF2H7 protein is prominently induced in neurons in the peri-infarction region. Furthermore, in a neuroblastoma cell line, BBF2H7 overexpression suppresses ER stress-induced cell death, while small interfering RNA knockdown of BBF2H7 promotes ER stress-induced cell death. Taken together, our results suggest that BBF2H7 is a novel ER stress transducer and could play important roles in preventing accumulation of unfolded proteins in damaged neurons.
authors.affiliation: Division of Molecular and Cellular Biology, Department of Anatomy, Faculty of Medicine, University of Miyazaki, Kihara 5200, Kiyotake, Miyazaki 889-1692, Japan. sh-kondo@med.miyazaki-u.ac.jp
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kondo
authors.forename: Atsushi
authors.initials: A
authors.lastname: Saito
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Hino
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Murakami
authors.forename: Maiko
authors.initials: M
authors.lastname: Ogata
authors.forename: Soshi
authors.initials: S
authors.lastname: Kanemoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nara
authors.forename: Akinori
authors.initials: A
authors.lastname: Yamashita
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yoshinaga
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
authors.forename: Kazunori
authors.initials: K
authors.lastname: Imaizumi
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000502:physiology*; D002545:Brain Ischemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D024202:Electrophoretic Mobility Shift Assay; D004721:Endoplasmic Reticulum / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology; D019084:Fluorescent Antibody Technique, Indirect; D017930:Genes, Reporter; D005910:Glioma / Q000473:pathology; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D008156:Luciferases / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D051381:Rats; D013314:Stress, Mechanical
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C518609:CREB3L2 protein, human; D008156:Luciferases