Signalling mediated by the endoplasmic reticulum stress transducer OASIS is involved in bone formation
- 20 September 2009
- journal article
- letter
- Published by Springer Science and Business Media LLC in Nature
- Vol. 11 (10), 1205-1211
- https://doi.org/10.1038/ncb1963
Abstract
Eukaryotic cells have signalling pathways from the endoplasmic reticulum (ER) to cytosol and nuclei, to avoid excess accumulation of unfolded proteins in the ER. We previously identified a new type of ER stress transducer, OASIS, a bZIP (basic leucine zipper) transcription factor, which is a member of the CREB/ATF family and has a transmembrane domain1,2,3,4,5,6. OASIS is processed by regulated intramembrane proteolysis (RIP) in response to ER stress, and is highly expressed in osteoblasts. OASIS−/− mice exhibited severe osteopenia, involving a decrease in type I collagen in the bone matrix and a decline in the activity of osteoblasts, which showed abnormally expanded rough ER, containing of a large amount of bone matrix proteins. Here we identify the gene for type 1 collagen, Col1a1, as a target of OASIS, and demonstrate that OASIS activates the transcription of Col1a1 through an unfolded protein response element (UPRE)-like sequence in the osteoblast-specific Col1a1 promoter region. Moreover, expression of OASIS in osteoblasts is induced by BMP2 (bone morphogenetic protein 2), the signalling of which is required for bone formation. Additionally, RIP of OASIS is accelerated by BMP2 signalling, which causes mild ER stress. Our studies show that OASIS is critical for bone formation through the transcription of Col1a1 and the secretion of bone matrix proteins, and they reveal a new mechanism by which ER stress-induced signalling mediates bone formation.Keywords
This publication has 34 references indexed in Scilit:
- Regulation of endoplasmic reticulum stress response by a BBF2H7-mediated Sec23a pathway is essential for chondrogenesisNature, 2009
- A Novel ER Stress Transducer, OASIS, Expressed in AstrocytesAntioxidants and Redox Signaling, 2007
- BBF2H7, a Novel Transmembrane bZIP Transcription Factor, Is a New Type of Endoplasmic Reticulum Stress TransducerMolecular and Cellular Biology, 2007
- Prolyl 3-hydroxylase 1 deficiency causes a recessive metabolic bone disorder resembling lethal/severe osteogenesis imperfectaNature Genetics, 2007
- The testes‐specific bZip type transcription factor Tisp40 plays a role in ER stress responses and chromatin packaging during spermiogenesisGenes to Cells, 2006
- Type I Collagen in Hsp47-null Cells Is Aggregated in Endoplasmic Reticulum and Deficient in N-Propeptide Processing and FibrillogenesisD⃞Molecular Biology of the Cell, 2006
- Cleavage of the membrane‐bound transcription factor OASIS in response to endoplasmic reticulum stressJournal of Neurochemistry, 2006
- Cooperative Interactions between Activating Transcription Factor 4 and Runx2/Cbfa1 Stimulate Osteoblast-specific Osteocalcin Gene ExpressionPublished by Elsevier BV ,2005
- Differential Contributions of ATF6 and XBP1 to the Activation of Endoplasmic Reticulum Stress-Responsive cis-Acting Elements ERSE, UPRE and ERSE-IIThe Journal of Biochemistry, 2004
- XBP1, Downstream of Blimp-1, Expands the Secretory Apparatus and Other Organelles, and Increases Protein Synthesis in Plasma Cell DifferentiationImmunity, 2004