RRC ID 4221
著者 Deng X, Yin X, Allan R, Lu DD, Maurer CW, Haimovitz-Friedman A, Fuks Z, Shaham S, Kolesnick R.
タイトル Ceramide biogenesis is required for radiation-induced apoptosis in the germ line of C. elegans.
ジャーナル Science
Abstract Ceramide engagement in apoptotic pathways has been a topic of controversy. To address this controversy, we tested loss-of-function (lf) mutants of conserved genes of sphingolipid metabolism in Caenorhabditis elegans. Although somatic (developmental) apoptosis was unaffected, ionizing radiation-induced apoptosis of germ cells was obliterated upon inactivation of ceramide synthase and restored upon microinjection of long-chain natural ceramide. Radiation-induced increase in the concentration of ceramide localized to mitochondria and was required for BH3-domain protein EGL-1-mediated displacement of CED-4 (an APAF-1-like protein) from the CED-9 (a Bcl-2 family member)/CED-4 complex, an obligate step in activation of the CED-3 caspase. These studies define CEP-1 (the worm homolog of the tumor suppressor p53)-mediated accumulation of EGL-1 and ceramide synthase-mediated generation of ceramide through parallel pathways that integrate at mitochondrial membranes to regulate stress-induced apoptosis.
巻・号 322(5898)
ページ 110-5
公開日 2008-10-3
DOI 10.1126/science.1158111
PII 322/5898/110
PMID 18832646
PMC PMC2585063
MeSH Animals Apoptosis* Caenorhabditis elegans / cytology* Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans / physiology Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Calcium-Binding Proteins / genetics Calcium-Binding Proteins / metabolism Ceramides / biosynthesis Ceramides / metabolism* Ceramides / pharmacology Genes, Helminth Germ Cells / cytology* Germ Cells / metabolism Germ Cells / radiation effects Mitochondria / metabolism Mitochondrial Membranes / metabolism Mutation Nuclear Envelope / metabolism Oxidoreductases / genetics Oxidoreductases / metabolism Proto-Oncogene Proteins c-abl / genetics Proto-Oncogene Proteins c-abl / metabolism Proto-Oncogene Proteins c-bcl-2 / metabolism Radiation, Ionizing* Repressor Proteins / metabolism Tumor Suppressor Protein p53 / metabolism
IF 41.846
引用数 123
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
線虫 tm470 tm2384 tm2178