The seven faces of SIRT7

Abstract

SIRT7, a member of the sirtuin family of NAD⁺-dependent protein deacetylases, is a key mediator of many cellular activities. SIRT7 expression is linked to cell proliferation and oncogenic activity, connecting SIRT7-dependent regulation of ribosome biogenesis with checkpoints controlling cell cycle progression, metabolic homeostasis, stress resistance, aging and tumorigenesis. Despite this important functional link, the enzymatic activity, the molecular targets and physiological functions of SIRT7 are poorly defined. Here, we review recent progress in SIRT7 research and elaborate the main pathways in which SIRT7 participates.

Keywords: SIRT7; metabolism; stress response; transcription; tumorigenesis.

Figure 1.

The sirtuin family of NAD⁺-dependent deacetylases. The seven mammalian sirtuins (SIRT1–7) share a conserved catalytic core domain (HDAC domain) with varying N- and C-terminal sequences. They localize to different cellular compartments, use NAD⁺ as a co-factor and serve functions in multiple cellular processes.

Figure 2.

Reversible acetylation of PAF53 and U3–55k regulates pre-rRNA synthesis and processing. In normal growth conditions, SIRT7 keeps the Pol I-associated factor PAF53 hypoacetylated, which is required for rDNA transcription. Deacetylation of the U3–55k protein by SIRT7 facilitates the interaction of U3–55k with U3 snoRNA, thus promoting pre-rRNA cleavage. Nucleolar release of SIRT7 in response to environmental or metabolic stress enhances acetylation of PAF53 and U3–55k, which impairs Pol I transcription and pre-rRNA processing and attenuates ribosome biogenesis.

Figure 3.

The seven faces of SIRT7. The cartoon depicts the main pathways in which SIRT7 is involved. The proteins that are targeted by SIRT7 or mediate SIRT7 function are highlighted.