RRC ID 3630
著者 Schertel C, Conradt B.
タイトル C. elegans orthologs of components of the RB tumor suppressor complex have distinct pro-apoptotic functions.
ジャーナル Development
Abstract To obtain insight into the role of the retinoblastoma susceptibility gene (Rb; also known as Rb1) in apoptosis, we analyzed Caenorhabditis elegans mutants lacking a functional lin-35 RB gene. We found that the loss of lin-35 function results in a decrease in constitutive germ cell apoptosis. We present evidence that lin-35 promotes germ cell apoptosis by repressing the expression of ced-9, an anti-apoptotic C. elegans gene that is orthologous to the human proto-oncogene BCL2. Furthermore, we show that the genes dpl-1 DP, efl-1 E2F and efl-2 E2F also promote constitutive germ cell apoptosis. However, in contrast to lin-35, dpl-1 (and probably also efl-1 and efl-2) promotes germ cell apoptosis by inducing the expression of the pro-apoptotic genes ced-4 and ced-3, which encode an APAF1-like adaptor protein and a pro-caspase, respectively. Based on these results, we propose that C. elegans orthologs of components of the RB tumor suppressor complex have distinct pro-apoptotic functions in the germ line and that the transcriptional regulation of components of the central apoptosis machinery is a critical determinant of constitutive germ cell apoptosis in C. elegans. Finally, we demonstrate that lin-35, dpl-1 and efl-2, but not efl-1, function either downstream of or in parallel to cep-1 p53 (also known as TP53) and egl-1 BH3-only to cause DNA damage-induced germ cell apoptosis. Our results have implications for the general mechanisms through which RB-like proteins control gene expression, the role of RB-, DP- and E2F-like proteins in apoptosis, and the regulation of apoptosis.
巻・号 134(20)
ページ 3691-701
公開日 2007-10-1
DOI 10.1242/dev.004606
PII dev.004606
PMID 17881492
MeSH Animals Animals, Genetically Modified Apoptosis / physiology* Caenorhabditis elegans / anatomy & histology Caenorhabditis elegans / embryology Caenorhabditis elegans / genetics* Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Calcium-Binding Proteins / genetics Calcium-Binding Proteins / metabolism DNA Damage E2F Transcription Factors / genetics E2F Transcription Factors / metabolism Germ Cells / cytology Germ Cells / physiology* Humans Protein Isoforms / genetics Protein Isoforms / metabolism* Proto-Oncogene Mas Proto-Oncogene Proteins c-bcl-2 / genetics Proto-Oncogene Proteins c-bcl-2 / metabolism RNA Interference RNA, Messenger / metabolism Retinoblastoma Protein / genetics Retinoblastoma Protein / metabolism* Transcription Factors / genetics Transcription Factors / metabolism
IF 5.611
引用数 46
WOS 分野 DEVELOPMENTAL BIOLOGY
リソース情報
線虫 tm2359