Cerulenin-mediated apoptosis is involved in adenine metabolic pathway

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Cerulenin-mediated apoptosis is involved in adenine metabolic pathway
Kyung Sook Chung; N K Sun; S H Lee; H J Lee; Shin Jung Choi; S K Kim; J H Song; Y J Jang; K B Song; Hyang Sook Yoo; J Simon; Mi Sun Won
Bibliographic Citation
Biochemical and Biophysical Research Communications, vol. 349, no. 3, pp. 1025-1031
Publication Year
Cerulenin, a fatty acid synthase (FAS) inhibitor, induces apoptosis of variety of tumor cells. To elucidate mode of action by cerulenin, we employed the proteomics approach using Schizosaccharomyces pombe. The differential protein expression profile of S. pombe revealed that cerulenin modulated the expressions of proteins involved in stresses and metabolism, including both ade10 and adk1 proteins. The nutrient supplementation assay demonstrated that cerulenin affected enzymatic steps transferring a phosphoribosyl group. This result suggests that cerulenin accumulates AMP and p-ribosyl-s-amino-imidazole carboxamide (AICAR) and reduces other necessary nucleotides, which induces feedback inhibition of enzymes and the transcriptional regulation of related genes in de novo and salvage adenine metabolic pathway. Furthermore, the deregulation of adenine nucleotide synthesis may interfere ribonucleotide reductase and cause defects in cell cycle progression and chromosome segregation. In conclusion, cerulenin induces apoptosis through deregulation of adenine nucleotide biosynthesis resulting in nuclear division defects in S. pombe.
Ade10AdenineAdk1AICARCeruleninFASFas2/lsd1Fission yeast
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Division of Research on National Challenges > 1. Journal Articles
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
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