NAD-dependent protein deacetylase sirtuin-7 (SIRT7) (SIRT7)

NAD-dependent protein deacetylase sirtuin-7 (SIRT7) is a member of the sirtuin family of Class III histone deacetylases, primarily localized within the nucleolus (UniProt). It plays a fundamental role in cellular homeostasis by regulating ribosome biogenesis through the activation of RNA polymerase I-mediated transcription (PMC). Beyond its nucleolar functions, SIRT7 is a key guardian of genomic integrity, facilitating DNA damage repair and maintaining heterochromatin stability (PubMed). It also acts as a metabolic sensor, modulating mitochondrial function and lipid metabolism by deacetylating various non-histone substrates such as GABPβ1 and ATM (UniProt, PMC). In clinical contexts, SIRT7 is frequently upregulated in numerous malignancies, including hepatocellular carcinoma and breast cancer, where it promotes tumor growth, metastasis, and resistance to chemotherapy (PMC, PubMed). Conversely, its deficiency is linked to accelerated aging, cardiac hypertrophy, and metabolic dysfunction, highlighting its complex, context-dependent biological roles (PMC). Consequently, SIRT7 has emerged as a promising therapeutic target, with several small-molecule inhibitors currently under preclinical investigation for cancer treatment (Frontiers).

Other names

Sirtuin 7SIR2L7SIR2-like protein 7NAD-dependent protein deacylase sirtuin-7Regulatory protein SIR2 homolog 7Sir2-related protein type 7Sirtuin type 7

Inhibition of NAD+-dependent deacetylation and deacylation activities, specifically targeting H3K18Ac and non-histone substrates like ATM and GABPβ1 to disrupt oncogenic signaling, ribosome biogenesis, and DNA repair mechanisms (Frontiers, PMC).