Physiological unfolded protein response regulated by OASIS family members, transmembrane bZIP transcription factors

Abstract

SummaryThe endoplasmic reticulum (ER) plays role in the maintenance of numerous aspects of cellular and organismal homeostasis by folding, modifying, and exporting nascent secretory and transmembrane proteins. Failure of the ER's adaptive capacity results in accumulation of unfolded or malfolded proteins in the ER lumen (ER stress). To avoid cellular damage, mammalian cells activate the specific signals from the ER to the cytosol or nucleus to enhance the capacity for protein folding, attenuate the synthesis of proteins, and degrade unfolded proteins. These signaling pathways are collectively known as the unfolded protein response (UPR). The canonical branches of the UPR are mediated by three ER membrane-bound proteins, PERK, IRE1, and ATF6. These ER stress transducers basically play important roles in cell survival after ER stress. Recently, novel types of ER stress transducers, OASIS family members that share a region of high sequence similarity with ATF6 have been identified. They have a transmembrane domain, which allows them to associate with the ER, and possess a transcription-activation domain and a bZIP domain. OASIS family proteins include OASIS, BBF2H7, CREBH, AIbZIP, and Luman. Despite the structural similarities among OASIS family proteins and ATF6, differences in activating stimuli, tissue distribution, and response element binding indicate specialized functions of each member on regulating the UPR in the specific organs and tissues. Here, we summarize our current understanding of biochemical characteristics and in vivo functions of OASIS family proteins, particularly focusing on OASIS and BBF2H7. A growing body of new works suggests that the UPR branches regulated by OASIS family members play essential roles in cell differentiation and maturation or maintenance of basal cellular homeostasis in mammals.

Nuclear Matrix Protein 4 Is a Novel Regulator of Ribosome Biogenesis and Controls the Unfolded Protein Response via Repression of Gadd34 Expression

“…Oasis is another transcription factor closely related to ATF6 that is also activated via regulated intramembrane proteolysis during ER stress (12). Together the ATF4, XBP1, ATF6, and Oasis transcription factors serve to enhance expression of UPR genes involved in protein folding and assembly, vesicular transport, ER and Golgi expansion, and degradation of unfolded proteins (1,12 3 The abbreviations used are: ER, endoplasmic reticulum; UPR, unfolded protein response; eIF2␣-P, phosphorylation of the ␣ subunit of eIF2; MSPC, mesenchymal stem progenitor cell; qPCR, quantitative PCR; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. …”

“…In response to ER stress, ATF6 is transported from the ER to Golgi for proteolytic cleavage that allows for release of the amino-terminal portion of ATF6 to enter the nucleus and direct transcription of targeted UPR genes (1). Oasis is another transcription factor closely related to ATF6 that is also activated via regulated intramembrane proteolysis during ER stress (12). Together the ATF4, XBP1, ATF6, and Oasis transcription factors serve to enhance expression of UPR genes involved in protein folding and assembly, vesicular transport, ER and Golgi expansion, and degradation of unfolded proteins (1,12).…”

“…Oasis is another transcription factor closely related to ATF6 that is also activated via regulated intramembrane proteolysis during ER stress (12). Together the ATF4, XBP1, ATF6, and Oasis transcription factors serve to enhance expression of UPR genes involved in protein folding and assembly, vesicular transport, ER and Golgi expansion, and degradation of unfolded proteins (1,12). Hence the UPR provides for key transcriptional, translational, and proteolytic processes that are central to professional secretory cells.…”

Molecular Mechanism of Endoplasmic Reticulum Stress Transducer OASIS Family

“…ER stress in osteoblasts induced by the BMP2 signalling pathway is associated with a high demand for synthesis and secretion of bone matrix proteins. Activated OASIS directly binds to the CRE-like sequence in the Col1a1 promoter region and induces its transcription in osteoblasts for osteogenesis [13]. (Fig.…”

Unfolded protein response, activated by OASIS family transcription factors, promotes astrocyte differentiation

“…In mammalian cells, the three major transducers of the UPR are PKR-like endoplasmic reticulum kinase 3 , inositol-requiring 1 (refs 4,5), and activating transcription factor 6 (ATF6) 6,7 . Additionally, novel types of ER stress transducers that are structurally included in the CREB/ATF family and share a region of high sequence similarity with ATF6 have been identified 8,9 . These proteins have a transmembrane domain, which allows them to associate with the ER, a transcription-activation domain and a basic leucine zipper (bZIP) domain.…”