SAT2 Human

Spermidine/spermine N1-acetyltransferase 2, commonly referred to as SSAT2, is a critical enzyme involved in the regulation of polyamine metabolism. Polyamines, including spermine, spermidine, and putrescine, are essential for various cellular functions such as DNA stabilization, protein synthesis, and cell proliferation . SSAT2 plays a pivotal role in maintaining the homeostasis of these polyamines by catalyzing their acetylation, which facilitates their degradation or export from the cell .

The enzyme was first identified in mammalian cells, where it was observed to be a key regulator in the polyamine catabolic pathway . SSAT2 is inducible by polyamines and polyamine analogues, making it a crucial component in the cellular response to polyamine levels . Its activity is typically low under normal physiological conditions but can be significantly upregulated in response to various stimuli, including oxidative stress and tumorigenesis .

SSAT2 catalyzes the N1-acetylation of spermidine and spermine, converting them into their respective acetylated forms . This acetylation process is a rate-limiting step in the catabolic pathway of polyamines, leading to their subsequent degradation by acetylpolyamine oxidase or their export out of the cell . By regulating the intracellular concentration of polyamines, SSAT2 helps prevent their overaccumulation, which can be cytotoxic.

Alterations in SSAT2 expression and activity have been linked to various types of cancer. During tumorigenesis, the enzyme’s expression levels can be significantly altered, leading to disruptions in polyamine homeostasis. These disruptions can induce cellular damage, including oxidative stress, cell cycle arrest, and DNA damage. Consequently, SSAT2 has been studied as a potential biomarker for cancer diagnosis and prognosis. Additionally, targeting SSAT2 and polyamine metabolism has been explored as a therapeutic strategy to enhance the efficacy of chemotherapy.

The modulation of SSAT2 activity presents a promising avenue for therapeutic intervention. Polyamine analogues that increase SSAT2 expression have shown potential in enhancing the cytotoxicity of chemotherapeutic agents. Furthermore, drugs targeting polyamine metabolism and SSAT2 expression are being investigated for their potential to develop into novel cancer treatments.