Overcoming metabolic stress is a critical step in tumor growth. Acetyl coenzyme A (acetyl-CoA) generated from glucose and acetate uptake is important for histone acetylation and gene expression. However, how acetyl-CoA is produced under nutritional stress is unclear. We demonstrate here that glucose deprivation results in AMP-activated protein kinase (AMPK)-mediated acetyl-CoA synthetase 2 (ACSS2) phosphorylation at S659, which exposed the nuclear localization signal of ACSS2 for importin α5 binding and nuclear translocation. In the nucleus, ACSS2 binds to transcription factor EB and translocates to lysosomal and autophagy gene promoter regions, where ACSS2 incorporates acetate generated from histone acetylation turnover to locally produce acetyl-CoA for histone H3 acetylation in these regions and promote lysosomal biogenesis, autophagy, cell survival, and brain tumorigenesis. In addition, ACSS2 S659 phosphorylation positively correlates with AMPK activity in glioma specimens and grades of glioma malignancy. These results underscore the significance of nuclear ACSS2-mediated histone acetylation in maintaining cell homeostasis and tumor development.
Pubmed ID: 28552616 RIS Download
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Software application with data analysis tools and spreadsheet templates to track and visualize data. It is used to manage and process data.
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View all literature mentionsThis polyclonal targets HIST1H3A
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View all literature mentionsThis monoclonal targets TFEB (C-6)
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View all literature mentionsCell line U-87MG ATCC is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets WIPI-1 (F-6)
View all literature mentionsThis monoclonal targets beta-glucuronidase (E-11)
View all literature mentionsThis monoclonal targets beta-glucosidase (C-2)
View all literature mentionsThis polyclonal targets HIST1H3A
View all literature mentionsThis polyclonal targets HIST1H2BA
View all literature mentionsThis polyclonal targets ATP citrate lyase
View all literature mentionsThis unknown targets Cathepsin A
View all literature mentionsThis monoclonal targets TFEB (C-6)
View all literature mentionsThis polyclonal targets LAMP1
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets TUBA3E, TUBA4A, TUBA8, TUBA3C, TUBA1C, TUBA1B, TUBA3D, TUBA1A
View all literature mentionsThis monoclonal targets GST (B-14)
View all literature mentionsThis polyclonal targets LC3B
View all literature mentionsThis monoclonal targets Calpain-1 Domain III Mouse mAb (9A4H8D3)
View all literature mentionsThis monoclonal targets Acaca
View all literature mentionsThis monoclonal targets AMPK-alpha, phospho (Thr172)
View all literature mentionsThis monoclonal targets AMPK alpha
View all literature mentionsThis polyclonal targets Histone H3 (asymmetric di methyl R17) - ChIP Grade
View all literature mentionsThis monoclonal targets PCNA
View all literature mentionsThis polyclonal targets acetyl-Histone H4
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