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Sirtuin 7 (SIRT7)
- Target
- SIRT7
- Molecular classification
- Enzyme, NAD+-dependent deacetylase, Histone deacetylase (class III), Chromatin modifier, Epigenetic regulator
01
Overview
Sirtuin 7 is an NAD+-dependent class III histone deacetylase of the sirtuin family, primarily localized in the nucleolus[3][7]. It specifically deacetylates histone H3 at lysine 18 and lysine 36, impacting chromatin structure, gene expression, and DNA repair[1][4]. SIRT7 is essential for maintaining rDNA stability, regulating ribosome biogenesis, and ensuring global genomic integrity. It also modulates mitochondrial function, RNA processing, and cellular senescence. SIRT7 displays context-dependent roles in cancer, acting either as an oncogene or tumor suppressor depending on the cellular environment[2][4]. As a chromatin-modifying enzyme, SIRT7 has emerged as a promising therapeutic target for cancer and age-related diseases, though specific, clinically approved modulators remain under investigation[2][8].
- Other names
- Sirtuin-7 (SIRT7)Silent information regulator 2-like protein 7Sirt7
02
Mechanism of action
Inhibition: Blocks SIRT7 deacetylase activity, altering chromatin acetylation, gene expression, and related cellular functions[8]. Activation: Promotes deacetylase function, affecting DNA repair, gene silencing, and rDNA stability[2][4].
03
Biological functions
Chromatin remodelingHistone deacetylation (notably H3K18 and H3K36)Regulation of gene expression and rDNA transcriptionDNA repair and genomic stabilityMitochondrial homeostasisRNA metabolism and splicingRegulation of cell proliferation and cellular senescence
04
Disease associations
Cancer (oncogenic or tumor suppressor, context-dependent)Aging and cellular senescenceMetabolic diseases (e.g. fatty liver)Hematopoietic stem cell agingGenomic instability disorders
05
Safety considerations
Non-specific targeting of sirtuins may result in broad epigenetic and metabolic disruption[8].Impairment of SIRT7 may lead to increased genomic instability, DNA repair deficits, and mitochondrial dysfunction[3][7].
06
Interacting drugs
There are no approved drugs that selectively target Sirtuin 7, but small molecule modulators (inhibitors/activators) are under investigation; general sirtuin inhibitors (e.g., nicotinamide, sirtinol) may affect SIRT7 among other family members[8][2].
07
Biomarkers
Acetylation status of H3K18 and H3K36 in tumor or tissue samples may reflect SIRT7 activity[1][4].SIRT7 expression levels in cancers (e.g., breast, colorectal, gastric) have prognostic value[4].
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