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| Status |
Public on Dec 21, 2016 |
| Title |
A Homeostatic Shift Facilitates Endoplasmic Reticulum Proteostasis through Transcriptional Integration of Proteostatic Stress Response Pathways [expression] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
Gene expression in the liver obtained from Nrf1 CKO and control mice. Nrf1flox/flox::CYP1A1-Cre mice subcutaneously injected with 40 mg/kg body weight of 3-methylcholanthrene (3MC) were used as Nrf1 CKO mice, while Nrf1flox/flox mice similarly treated with 3MC were used as control mice. Livers were obtained 2 weeks after the 3MC injection.
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| Contributor(s) |
Baird L, Tsujita T, Kobayashi EH, Funayama R, Nagashima T, Nakayama K, Yamamoto M |
| Citation(s) |
27920251 |
| Submission date |
Oct 30, 2016 |
| Last update date |
Feb 02, 2018 |
| Contact name |
Eri H Kobayashi |
| Organization name |
Tohoku University Graduate School of Medicine
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| Department |
Medical Biochemistry
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| Street address |
2-1 Seiryo-machi, Aobaku
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| City |
Sendai |
| State/province |
Miyagi |
| ZIP/Postal code |
980-8575 |
| Country |
Japan |
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| Platforms (1) |
| GPL10787 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Probe Name version) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA351746 |
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