期刊
NATURE COMMUNICATIONS
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms12497
关键词
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资金
- National Natural Science Foundation of China [81372146, 31201044, 31171361, 31071248]
- Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant [20152524]
Maintenance of energy homeostasis is essential for cell survival. Here, we report that the ATP- and ubiquitin-independent REG gamma-proteasome system plays a role in maintaining energy homeostasis and cell survival during energy starvation via repressing rDNA transcription, a major intracellular energy-consuming process. Mechanistically, REG gamma-proteasome limits cellular rDNA transcription and energy consumption by targeting the rDNA transcription activator SirT7 for ubiquitin-independent degradation under normal conditions. Moreover, energy starvation induces an AMPK-directed SirT7 phosphorylation and subsequent REG gamma-dependent SirT7 subcellular redistribution and degradation, thereby further reducing rDNA transcription to save energy to overcome cell death. Energy starvation is a promising strategy for cancer therapy. Our report also shows that REG gamma knockdown markedly improves the anti-tumour activity of energy metabolism inhibitors in mice. Our results underscore a control mechanism for an ubiquitin-independent process in maintaining energy homeostasis and cell viability under starvation conditions, suggesting that REG gamma-proteasome inhibition has a potential to provide tumour-starving benefits.
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