Details

Autor(en) / Beteiligte

• Sun, Lianhui
• Fan, Guangjian
• Shan, Peipei
• Qiu, Xiaoying
• Dong, Shuxian
• Liao, Lujian
• Yu, Chunlei
• Wang, Tingting
• Gu, Xiaoyang
• Li, Qian
• Song, Xiaoyu
• Cao, Liu
• Li, Xiaotao
• Cui, Yongping
• Zhang, Shengping
• Wang, Chuangui

Titel

Regulation of energy homeostasis by the ubiquitin-independent REGγ proteasome

Ist Teil von

• Nature communications, 2016-08, Vol.7 (1), p.12497-12497, Article 12497

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2016

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Maintenance of energy homeostasis is essential for cell survival. Here, we report that the ATP- and ubiquitin-independent REGγ-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, REGγ-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 REGγ-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 REGγ 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 REGγ-proteasome inhibition has a potential to provide tumour-starving benefits.