Spermidine/Spermine-N1-Acetyltransferase: A Key Metabolic Regulator

March 2008 in “ AJP Endocrinology and Metabolism ”

Anthony E. Pegg

spermidine spermine N1-acetyltransferase SSAT polyamine ATP acetyl-CoA hypoxia-inducible factor-1 alpha NF-kappaB

Studysummary This article reviews the regulation and roles of spermidine/spermine-N(1)-acetyltransferase (SSAT) in polyamine metabolism and its potential as a target in cancer and other diseases, without reporting new experimental results.

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The document described spermidine/spermine-N1-acetyltransferase (SSAT) as a crucial enzyme in polyamine metabolism, influencing cellular growth and homeostasis. SSAT was highly regulated and inducible, with its activity linked to conditions like cancer, obesity, and stress response. It played a role in therapeutic strategies, particularly in cancer treatment, by mediating polyamine depletion. Transgenic studies showed SSAT's impact on physiological processes, including hair loss and altered lipid metabolism. The enzyme's regulation involved transcriptional and post-transcriptional mechanisms, with polyamines enhancing its expression and stability. Despite challenges in targeting polyamine metabolism for cancer therapy, SSAT's complex role suggested potential therapeutic applications, necessitating further research to understand its broader impact on cellular processes.

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research Genetically Altered Expression of Spermidine/Spermine N1-Acetyltransferase Affects Fat Metabolism in Mice via Acetyl-CoA

128 citations , December 2006 in “Journal of Biological Chemistry”

This study found that overexpression of the enzyme spermidine/spermine N1-acetyltransferase in mice was associated with increased fat oxidation and a leaner phenotype, while knock-out mice exhibited increased fat accumulation.

research Activated Polyamine Catabolism Depletes Acetyl-CoA Pools and Suppresses Prostate Tumor Growth in TRAMP Mice

91 citations , July 2004 in “Journal of Biological Chemistry”

This study found that overexpression of the enzyme SSAT in a mouse model significantly reduced prostate tumor size and progression, suggesting it could be a promising strategy against prostate cancer.

research Targeted Expression of Spermidine/Spermine N1-Acetyltransferase Increases Susceptibility to Chemically Induced Skin Carcinogenesis

54 citations , February 2002 in “Carcinogenesis”

This study suggests that activation of polyamine catabolism in K6-SSAT transgenic mice may significantly increase skin tumor development and progression to carcinomas following chemical induction.

research Relation of Skin Polyamines to the Hairless Phenotype in Transgenic Mice Overexpressing Spermidine/Spermine N1-Acetyltransferase

54 citations , May 2001 in “Journal of Investigative Dermatology”

This study suggests that increased putrescine levels may disrupt normal hair follicle development in transgenic mice, leading to hair loss and altered skin structure, yet these mice appear more resistant to skin tumorigenesis.

research Modulation of Murine Hair Follicle Function by Alterations in Ornithine Decarboxylase Activity

71 citations , May 1996 in “Journal of Investigative Dermatology”

This study found that overexpression of a mutated ornithine decarboxylase transgene in mice led to complete hair loss, which could be prevented or reversed with an ODC inhibitor.