日本語フィールド
著者：Baird, Liam; Tsujita, Tadayuki; Kobayashi, Eri H.; Funayama, Ryo; Nagashima, Takeshi; Nakayama, Keiko; Yamamoto, Masayuki; Yamamoto, Masayuki題名：A homeostatic shift facilitates endoplasmic reticulum proteostasis through transcriptional integration of proteostatic stress response pathways発表情報：Molecular and Cellular Biology 巻: 37 号: 4 ページ: e00439-16キーワード：概要：Eukaryotic cells maintain protein homeostasis through the activity of multiple basal and inducible systems, which function in concert to allow cells to adapt to a wide range of environmental conditions. Although the transcriptional programs regulating individual pathways have been studied in detail, it is not known how the different pathways are transcriptionally integrated such that a deficiency in one pathway can be compensated by a change in an auxiliary response. One such pathway that plays an essential role in many proteostasis responses is the ubiquitin-proteasome system, which functions to degrade damaged, unfolded, or short half-life proteins. Transcriptional regulation of the proteasome is mediated by the transcription factor Nrf1. Using a conditional knockout mouse model, we found that Nrf1 regulates protein homeostasis in the endoplasmic reticulum (ER) through transcriptional regulation of the ER stress sensor ATF6. In Nrf1 conditional-knockout mice, a reduction in proteasome activity is accompanied by an ATF6-dependent downregulation of the endoplasmic reticulum-associated degradation machinery, which reduces the substrate burden on the proteasome. This indicates that Nrf1 regulates a homeostatic shift through which proteostasis in the endoplasmic reticulum and cytoplasm are coregulated based on a cell's ability to degrade proteins.抄録：英語フィールド
Author：Baird, Liam; Tsujita, Tadayuki; Kobayashi, Eri H.; Funayama, Ryo; Nagashima, Takeshi; Nakayama, Keiko; Yamamoto, Masayuki; Yamamoto, MasayukiTitle：A homeostatic shift facilitates endoplasmic reticulum proteostasis through transcriptional integration of proteostatic stress response pathwaysAnnouncement information:Molecular and Cellular Biology Vol: 37 Issue: 4 Page: e00439-16An abstract：Eukaryotic cells maintain protein homeostasis through the activity of multiple basal and inducible systems, which function in concert to allow cells to adapt to a wide range of environmental conditions. Although the transcriptional programs regulating individual pathways have been studied in detail, it is not known how the different pathways are transcriptionally integrated such that a deficiency in one pathway can be compensated by a change in an auxiliary response. One such pathway that plays an essential role in many proteostasis responses is the ubiquitin-proteasome system, which functions to degrade damaged, unfolded, or short half-life proteins. Transcriptional regulation of the proteasome is mediated by the transcription factor Nrf1. Using a conditional knockout mouse model, we found that Nrf1 regulates protein homeostasis in the endoplasmic reticulum (ER) through transcriptional regulation of the ER stress sensor ATF6. In Nrf1 conditional-knockout mice, a reduction in proteasome activity is accompanied by an ATF6-dependent downregulation of the endoplasmic reticulum-associated degradation machinery, which reduces the substrate burden on the proteasome. This indicates that Nrf1 regulates a homeostatic shift through which proteostasis in the endoplasmic reticulum and cytoplasm are coregulated based on a cell's ability to degrade proteins.