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SIRT6 transcriptionally regulates global protein synthesis through transcription factor Sp1 independent of its deacetylase activity.

Nucleic Acids Res. 2019; 
Ravi Venkatraman,Jain Aditi,Khan Danish,Ahamed Faiz,Mishra Sneha,Giri Malyasree,Inbaraj Meena,Krishna Swati,Sarikhani Mohsen,Maity Sangeeta,Kumar Shweta,Shah Riyaz Ahmad,Dave Pratik,Pandit Anwit S,Rajendran Rajprabu,Desingu Perumal A,Varshney Umesh,Das Saumitra,Kolthur-Seetharam Ullas,Rajakumari Sona,Singh Mahavir,Sundaresan Nagaling
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Nucleic Acid Purification & Analysis For generation of stable Sp1 knockout cell line, gRNA targeting Sp1 cloned in plentiCRISPR v2 vector was obtained from GenScript® Get A Quote

摘要

Global protein synthesis is emerging as an important player in the context of aging and age-related diseases. However, the intricate molecular networks that regulate protein synthesis are poorly understood. Here, we report that SIRT6, a nuclear-localized histone deacetylase represses global protein synthesis by transcriptionally regulating mTOR signalling via the transcription factor Sp1, independent of its deacetylase activity. Our results suggest that SIRT6 deficiency increases protein synthesis in mice. Further, multiple lines of in vitro evidence suggest that SIRT6 negatively regulates protein synthesis in a cell-autonomous fashion and independent of its catalytic activity. Mechanistically, SIRT... More

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