title: Cerulenin-mediated apoptosis is involved in adenine metabolic pathway.
abstract: 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.
authors.affiliation: Biopharmaceutical Division, KRIBB, 52 Oun-dong, Yusong-gu, Daejeon 305-806, Republic of Korea.
authors.forename: Kyung-Sook
authors.initials: KS
authors.lastname: Chung
authors.forename: Nam-Kyu
authors.initials: NK
authors.lastname: Sun
authors.forename: Seung-Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Hyun-Jee
authors.initials: HJ
authors.lastname: Lee
authors.forename: Shin-Jung
authors.initials: SJ
authors.lastname: Choi
authors.forename: Sun-Kyung
authors.initials: SK
authors.lastname: Kim
authors.forename: Ju-Hyun
authors.initials: JH
authors.lastname: Song
authors.forename: Young-Joo
authors.initials: YJ
authors.lastname: Jang
authors.forename: Kyung-Bin
authors.initials: KB
authors.lastname: Song
authors.forename: Hyang-Sook
authors.initials: HS
authors.lastname: Yoo
authors.forename: Julian
authors.initials: J
authors.lastname: Simon
authors.forename: Misun
authors.initials: M
authors.lastname: Won
mesh_terms: D000225:Adenine / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D002569:Cerulenin / Q000494:pharmacology*; D020090:Chromosome Segregation / Q000187:drug effects; D048749:Cytokinesis / Q000187:drug effects; D015966:Gene Expression Regulation, Fungal; D040081:Protein Array Analysis; D012568:Schizosaccharomyces / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D002569:Cerulenin; D000225:Adenine