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Title 

Cerulenin-mediated apoptosis is involved in adenine metabolic pathway

Authors 

Kyung Sook ChungN K SunS H LeeH J LeeShin Jung ChoiS K KimJ H SongY J JangK B SongHyang Sook YooJ SimonMi Sun Won

Publisher 

Elsevier

Issue Date 

2006

Citation 

Biochemical and Biophysical Research Communications, vol. 349, no. 3, pp. 1025-1031

Keywords 

Ade10adenineAdk1AICARceruleninFASFas2/lsd1fission yeastapoptosis

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.

ISSN 

0006-291X

Link 

http://dx.doi.org/10.1016/j.bbrc.2006.08.130

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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