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C. elegans orthologs of components of the RB tumor suppressor complex have distinct pro-apoptotic functions.
Development. 2007 Oct; 134(20):3691-701.D

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.

Authors+Show Affiliations

Dartmouth Medical School, Department of Genetics, Norris Cotton Cancer Center, 7400 Remsen, Hanover, NH 03755, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17881492

Citation

Schertel, Claus, and Barbara Conradt. "C. Elegans Orthologs of Components of the RB Tumor Suppressor Complex Have Distinct Pro-apoptotic Functions." Development (Cambridge, England), vol. 134, no. 20, 2007, pp. 3691-701.
Schertel C, Conradt B. C. elegans orthologs of components of the RB tumor suppressor complex have distinct pro-apoptotic functions. Development. 2007;134(20):3691-701.
Schertel, C., & Conradt, B. (2007). C. elegans orthologs of components of the RB tumor suppressor complex have distinct pro-apoptotic functions. Development (Cambridge, England), 134(20), 3691-701.
Schertel C, Conradt B. C. Elegans Orthologs of Components of the RB Tumor Suppressor Complex Have Distinct Pro-apoptotic Functions. Development. 2007;134(20):3691-701. PubMed PMID: 17881492.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - C. elegans orthologs of components of the RB tumor suppressor complex have distinct pro-apoptotic functions. AU - Schertel,Claus, AU - Conradt,Barbara, Y1 - 2007/09/19/ PY - 2007/9/21/pubmed PY - 2008/2/19/medline PY - 2007/9/21/entrez SP - 3691 EP - 701 JF - Development (Cambridge, England) JO - Development VL - 134 IS - 20 N2 - 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. SN - 0950-1991 UR - https://www.unboundmedicine.com/medline/citation/17881492/C__elegans_orthologs_of_components_of_the_RB_tumor_suppressor_complex_have_distinct_pro_apoptotic_functions_ L2 - http://dev.biologists.org/cgi/pmidlookup?view=long&pmid=17881492 DB - PRIME DP - Unbound Medicine ER -