title: Regulation of energy homeostasis by the ubiquitin-independent REGγ proteasome.
abstract: 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.
authors: Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China.|Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University, Shanghai 200241, China.
authors: Lianhui
authors: L
authors: Sun
authors: Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China.|Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University, Shanghai 200241, China.
authors: Guangjian
authors: G
authors: Fan
authors: Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China.|Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University, Shanghai 200241, China.
authors: Peipei
authors: P
authors: Shan
authors: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University, Shanghai 200241, China.
authors: Xiaoying
authors: X
authors: Qiu
authors: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University, Shanghai 200241, China.
authors: Shuxian
authors: S
authors: Dong
authors: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University, Shanghai 200241, China.
authors: Lujian
authors: L
authors: Liao
authors: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University, Shanghai 200241, China.
authors: Chunlei
authors: C
authors: Yu
authors: Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China.
authors: Tingting
authors: T
authors: Wang
authors: Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China.
authors: Xiaoyang
authors: X
authors: Gu
authors: School of Life Science &Technology, China Pharmaceutical University, Nanjing 210009, China.
authors: Qian
authors: Q
authors: Li
authors: Key Laboratory of Medical Cell Biology, College of Translational Medicine, China Medical University, Shenyang 110000, China.
authors: Xiaoyu
authors: X
authors: Song
authors: Key Laboratory of Medical Cell Biology, College of Translational Medicine, China Medical University, Shenyang 110000, China.
authors: Liu
authors: L
authors: Cao
authors: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University, Shanghai 200241, China.|Department of Molecular and Cellular Biology, Baylor College of Medicine. One Baylor Plaza, Houston, Texas 77030, USA.
authors: Xiaotao
authors: X
authors: Li
authors: Key Laboratory of Cellular Physiology Ministry of Education, Shanxi Medical University, Shanxi 030001, China.
authors: Yongping
authors: Y
authors: Cui
authors: Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China.
authors: Shengping
authors: S
authors: Zhang
authors: Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China.|Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University, Shanghai 200241, China.
authors: Chuangui
authors: C
authors: Wang
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000378:metabolism*; D002470:Cell Survival; D003593:Cytoplasm / Q000378:metabolism; D004275:DNA, Ribosomal / Q000378:metabolism; D045325:HCT116 Cells; D057809:HEK293 Cells; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008819:Mice, Nude; D009369:Neoplasms / Q000628:therapy*; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D001324:Autoantigens; D004275:DNA, Ribosomal; C099558:Ki antigen; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex