Online citations, reference lists, and bibliographies.
← Back to Search

C. Elegans Cell Survival Gene Ced-9 Encodes A Functional Homolog Of The Mammalian Proto-oncogene Bcl-2

M. Hengartner, H. Horvitz
Published 1994 · Biology, Medicine

Cite This
Download PDF
Analyze on Scholarcy
Share
The activity of the C. elegans gene ced-9 is required to protect cells that normally survive from undergoing programmed cell death. Here we describe the cloning and molecular characterization of this gene. ced-9 is an element of a polycistronic locus that also contains the gene cyt-1, which encodes a protein similar to cytochrome b560 of complex II of the mitochondrial respiratory chain. ced-9 encodes a 280 amino acid protein showing sequence and structural similarities to the mammalian proto-oncogene bcl-2. Overexpression of bcl-2 can mimic the protective effect of ced-9 on C. elegans cell death and can prevent the ectopic cell deaths that occur in ced-9 loss-of-function mutants. These results suggest that ced-9 and bcl-2 are homologs and that the molecular mechanism of programmed cell death has been conserved from nematodes to mammals.
This paper references
10.1126/SCIENCE.1470921
Prevention of programmed cell death in Caenorhabditis elegans by human bcl-2.
D. Vaux (1992)
10.1038/336638A0
A genetic pathway for the development of the Caenorhabditis elegans HSN motor neurons
C. Desai (1988)
Deregulated Bcl-2 gene expression selectively prolongs survival of growth factor-deprived hemopoietic cell lines.
G. Núñez (1990)
10.1002/j.1460-2075.1988.tb02791.x
Alternative promoters and exons, somatic mutation and deregulation of the Bcl‐2‐Ig fusion gene in lymphoma.
M. Seto (1988)
10.1016/S0092-8674(85)80070-2
Cloning the chromosomal breakpoint of t(14;18) human lymphomas: clustering around Jh on chromosome 14 and near a transcriptional unit on 18
A. Bakhshi (1985)
A second informational suppressor, SUP-7 X, in Caenorhabditis elegans.
R. Waterston (1981)
10.1093/NAR/20.16.4187
Isolation and characterization of the chicken bcl-2 gene: expression in a variety of tissues including lymphoid and neuronal organs in adult and embryo.
Y. Eguchi (1992)
10.1073/PNAS.83.14.5214
Analysis of the structure, transcripts, and protein products of bcl-2, the gene involved in human follicular lymphoma.
Y. Tsujimoto (1986)
10.1016/S0074-7696(08)62066-5
Animal mitochondrial DNA: structure and evolution.
D. Wolstenholme (1992)
10.1073/PNAS.88.16.6961
BCL2 protein is topographically restricted in tissues characterized by apoptotic cell death.
D. Hockenbery (1991)
10.1016/0012-1606(77)90158-0
Post-embryonic cell lineages of the nematode, Caenorhabditis elegans.
J. Sulston (1977)
10.1016/S0065-2776(08)60822-6
Programmed cell death in the immune system.
J. J. Cohen (1991)
10.1016/0012-1606(83)90201-4
The embryonic cell lineage of the nematode Caenorhabditis elegans.
J. Sulston (1983)
10.1101/GAD.7.2.216
Molecular characterization of the her-1 gene suggests a direct role in cell signaling during Caenorhabditis elegans sex determination.
M. D. Perry (1993)
10.1016/0092-8674(90)90494-Y
CeMyoD accumulation defines the body wall muscle cell fate during C. elegans embryogenesis
M. Krause (1990)
10.1038/356494A0
Caenorhabditis elegans gene ced-9 protects cells from programmed cell death
M. Hengartner (1992)
10.1016/0092-8674(91)90002-G
Programmed cell death: Apoptosis and oncogenesis
G. Williams (1991)
10.1038/361365A0
Bcl-2 blocks apoptosis in cells lacking mitochondrial DNA
M. D. Jacobson (1993)
10.1016/0092-8674(93)80065-M
Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair
D. Veis (1993)
10.1128/MCB.9.2.701
The bcl-2 candidate proto-oncogene product is a 24-kilodalton integral-membrane protein highly expressed in lymphoid cell lines and lymphomas carrying the t(14;18) translocation.
Z. Chen-Levy (1989)
10.1098/RSTB.1991.0015
On the nature of undead cells in the nematode Caenorhabditis elegans
J. White (1991)
10.1091/MBC.3.2.221
Temporal and spatial expression patterns of the small heat shock (hsp16) genes in transgenic Caenorhabditis elegans.
E. Stringham (1992)
10.1016/0092-8674(93)90509-O
Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programed cell death
Zoltán N. Oltval (1993)
10.1016/0022-2836(92)90708-R
Gene organization deduced from the complete sequence of liverwort Marchantia polymorpha mitochondrial DNA. A primitive form of plant mitochondrial genome.
K. Oda (1992)
10.1523/JNEUROSCI.13-10-04422.1993
Bcl-2 affects survival but not neuronal differentiation of PC12 cells
A. Batistatou (1993)
10.1038/356397A0
Social controls on cell survival and cell death
M. Raff (1992)
The genetics of Caenorhabditis elegans.
S. Brenner (1974)
10.1016/0092-8674(90)90346-G
The product of fem-1, a nematode sex-determining gene, contains a motif found in cell cycle control proteins and receptors for cell-cell interactions
A. Spence (1990)
10.1146/ANNUREV.CB.07.110191.003311
Mechanisms and functions of cell death.
R. Ellis (1991)
10.1016/0092-8674(86)90362-4
Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation
M. Cleary (1986)
10.1016/0092-8674(91)90362-3
bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship
A. Strasser (1991)
10.1056/NEJM198211113072002
Distinctive chromosomal abnormalities in histologic subtypes of non-Hodgkin's lymphoma.
J. Yunis (1982)
10.1038/359552A0
Apoptotic cell death induced by c-myc is inhibited by bcl-2
R. Bissonnette (1992)
10.1016/0092-8674(87)90593-9
A cell that dies during wild-type C. elegans development can function as a neuron in a ced-3 mutant
L. Avery (1987)
10.1038/359554A0
Cooperative interaction between c-myc and bcl-2 proto-oncogenes
A. Fanidi (1992)
The Caenorhabditis elegans cell death gene ced-4 encodes a novel protein and is expressed during the period of extensive programmed cell death.
J. Yuan (1992)
10.1038/348334A0
Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death
D. Hockenbery (1990)
10.1016/B978-0-12-372180-8.50014-7
10 – PRODUCTION OF SINGLE-STRANDED DNA BY ASYMMETRIC PCR
P. McCabe (1990)
Molecular genetics of the Caenorhabditis elegans heterochronic gene lin-14.
G. Ruvkun (1989)
10.1002/j.1460-2075.1991.tb04966.x
Efficient gene transfer in C.elegans: extrachromosomal maintenance and integration of transforming sequences.
C. Mello (1991)
10.1016/0092-8674(87)90613-1
A trans-spliced leader sequence on actin mRNA in C. elegans
M. Krause (1987)
10.1126/SCIENCE.6093263
Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation.
Y. Tsujimoto (1984)
10.1042/BJ2220519
Nucleotide sequence encoding the flavoprotein and hydrophobic subunits of the succinate dehydrogenase of Escherichia coli.
D. Wood (1984)
10.1111/j.1469-185X.1951.tb00774.x
CELL DEATHS IN NORMAL VERTEBRATE ONTOGENY
A. Glücksmann (1951)
10.1073/PNAS.89.16.7295
Overexpressed full-length human BCL2 extends the survival of baculovirus-infected Sf9 insect cells.
E. Alnemri (1992)
10.1038/335184A0
Genome linking with yeast artificial chromosomes
A. Coulson (1988)
10.1016/0092-8674(91)90361-2
bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes
C. Sentman (1991)
10.1002/BIES.950130809
YACs and the C. elegans genome.
A. Coulson (1991)
10.1002/NEU.480230919
Molecular genetics of cell death in the nematode Caenorhabditis elegans.
M. Driscoll (1992)
10.1002/EJI.1830210819
Germinal center cells express bcl‐2 protein after activation by signals which prevent their entry into apoptosis
Y. J. Liu (1991)
10.1016/0092-8674(93)90508-N
bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death
L. Boise (1993)
10.1016/0092-8674(86)90004-8
Genetic control of programmed cell death in the nematode C. elegans
H. Ellis (1986)
10.1038/335440A0
Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells
D. Vaux (1988)
Structural features in eukaryotic mRNAs that modulate the initiation of translation.
M. Kozak (1991)
10.1073/PNAS.90.8.3516
MCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to BCL2.
K. M. Kozopas (1993)
The multivulva phenotype of certain Caenorhabditis elegans mutants results from defects in two functionally redundant pathways.
E. Ferguson (1989)
10.1016/0092-8674(93)90230-N
The proto-oncogene bcl-2 can selectively rescue neurotrophic factor-dependent neurons from apoptosis
T. Allsopp (1993)
10.1016/0092-8674(93)80066-N
Bcl-2 functions in an antioxidant pathway to prevent apoptosis
D. Hockenbery (1993)
Structure-function analysis of the Bcl-2 oncoprotein. Addition of a heterologous transmembrane domain to portions of the Bcl-2 beta protein restores function as a regulator of cell survival.
S. Tanaka (1993)
Cytochrome b560 (QPs1) of mitochondrial succinate-ubiquinone reductase. Immunochemistry, cloning, and nucleotide sequencing.
L. Yu (1992)
10.1126/SCIENCE.1411528
Prevention of programmed cell death of sympathetic neurons by the bcl-2 proto-oncogene.
I. García (1992)
Chromosome abnormalities in poorly differentiated lymphocytic lymphoma.
S. Fukuhara (1979)
Bcl-2: an antidote to programmed cell death.
Korsmeyer Sj (1992)
10.1002/YEA.320080309
Molecular cloning and physical analysis of an 8·2 kb segment of chromosome XI of Saccharomyces cerevisiae reveals five tightly linked genes
P. Abraham (1992)
10.1016/0092-8674(93)90457-2
Molecular regulation of apoptosis: Genetic controls on cell death
G. Williams (1993)
10.1016/0092-8674(93)90139-H
Operons in C. elegans: Polycistronic mRNA precursors are processed by trans-splicing of SL2 to downstream coding regions
J. Spieth (1993)
10.1016/0092-8674(93)90485-9
The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1β-converting enzyme
J. Yuan (1993)
10.1016/0012-1606(90)90174-H
The Caenorhabditis elegans genes ced-3 and ced-4 act cell autonomously to cause programmed cell death.
J. Yuan (1990)
10.1101/087969176.15.163
Global Control Systems
S. Gottesman (1983)
10.1126/SCIENCE.8235659
Bcl-2 inhibition of neural death: decreased generation of reactive oxygen species.
D. J. Kane (1993)
Characterization of A1, a novel hemopoietic-specific early-response gene with sequence similarity to bcl-2.
E. Y. Lin (1993)
10.1016/0092-8674(87)90448-X
Molecular analysis of mbcl-2: Structure and expression of the murine gene homologous to the human gene involved in follicular lymphoma
M. Negrini (1987)
10.1016/0022-2836(83)90056-6
Actin gene family of Caenorhabditis elegans.
J. Files (1983)



This paper is referenced by
10.1083/jcb.200905070
The BCL-2–like protein CED-9 of C. elegans promotes FZO-1/Mfn1,2– and EAT-3/Opa1–dependent mitochondrial fusion
Stéphane G. Rolland (2009)
10.1101/cshperspect.a008672
Cellular mechanisms controlling caspase activation and function.
Amanda B. Parrish (2013)
10.18452/14833
Identifikation Apoptose-assoziierter Gene in B-Zellen und Charakterisierung des Genproduktes LAPTM5
Hauke Schneider (2003)
10.1016/S0959-437X(96)90007-6
Programmed cell death in invertebrates.
M. Hengartner (1996)
10.1016/S0092-8674(00)80092-6
An Alternatively Spliced C. elegans ced-4 RNA Encodes a Novel Cell Death Inhibitor
S. Shaham (1996)
10.1016/S1569-2590(08)60056-7
Retinoids and Apoptosis
Lixin Zhang (1997)
10.1093/TOXSCI/38.1.23
Mitochondria-mediated cell injury
K. Wallace (1997)
10.1128/MCB.18.5.2912
Commitment and Effector Phases of the Physiological Cell Death Pathway Elucidated with Respect to Bcl-2, Caspase, and Cyclin-Dependent Kinase Activities
K. Harvey (1998)
10.1016/S0962-8924(98)01321-X
Bcl-2-family proteins: the role of the BH3 domain in apoptosis.
A. Kelekar (1998)
10.1016/S0092-8674(00)81733-X
Apaf1 Is Required for Mitochondrial Pathways of Apoptosis and Brain Development
H. Yoshida (1998)
10.1007/978-0-585-37971-5_5
The Regulation of Apoptosis in Animal Cells
S. McKenna (1999)
10.1002/(SICI)1097-4695(199905)39:2<307::AID-NEU14>3.0.CO;2-9
Programmed cell death of an identified motoneuron examined in vivo: electrophysiological and morphological correlates.
A. Delorme (1999)
10.1038/sj.cdd.4400525
Apoptosis without caspases: an inefficient molecular guillotine?
C. Borner (1999)
Mutational analysis of the Caenorhabditis elegans cell-death gene ced-3.
S. Shaham (1999)
10.1007/978-3-0348-8482-2_15
Reactive oxygen species, nitric oxide and apoptosis
C. A. Bombeck (2000)
10.1016/S0065-2571(99)00030-8
Interactions between protein kinases and proteases in cellular signaling and regulation.
E. Krebs (2000)
10.1089/NEU.2000.17.801
Apoptosis: overview and signal transduction pathways.
D. Bredesen (2000)
10.1016/j.exger.2018.11.016
The anti-oxidation and anti-aging effects of Ganoderma lucidum in Caenorhabditis elegans
Vu Thi Cuong (2019)
10.1016/S0968-0004(00)01740-0
Life-or-death decisions by the Bcl-2 protein family.
J. Adams (2001)
10.1002/047120918X.EMB1209
Programmed Cell Death
N. McCarthy (2002)
Analyse der Funktion von Signaladaptoren zelltodvermittelnder Rezeptoren
R. Wilke (2003)
Oridonin induces apoptosis of HeLa cells via altering expression of Bcl-2/Bax and activating caspase-3/ICAD pathway.
C. Zhang (2004)
10.1016/B0-08-045044-X/00103-6
Small Animal Test Systems for Screening
M. Muda (2007)
10.22074/IJFS.2015.4614
Protective Effects of Thymoquinone against Methotrexate-Induced Germ Cell Apoptosis in Male Mice
Fatemeh Sheikhbahaei (2016)
10.1146/ANNUREV-CANCERBIO-050216-121933
Apoptosis and Cancer
A. Letai (2017)
10.1091/MBC.E02-10-0631
The tumor suppressor cybL, a component of the respiratory chain, mediates apoptosis induction.
Timur Albayrak (2003)
10.1105/tpc.014613
Dissection of Arabidopsis Bax Inhibitor-1 Suppressing Bax–, Hydrogen Peroxide–, and Salicylic Acid–Induced Cell Death Article, publication date, and citation information can be found at www.plantcell.org/cgi/doi/10.1105/tpc.014613.
M. Kawai-yamada (2004)
10.1084/JEM.186.12.1975
The E1B 19K/Bcl-2–binding Protein Nip3 is a Dimeric Mitochondrial Protein that Activates Apoptosis
G. Chen (1997)
Functional Features of Hyperactive DEG/ENaC Channels Involved in Cell Death
Cristina Matthewman (2017)
10.1074/JBC.270.26.15870
Molecular Cloning and Pro-apoptotic Activity of ICErelII and ICErelIII, Members of the ICE/CED-3 Family of Cysteine Proteases (*)
N. A. Munday (1995)
10.1083/JCB.130.1.157
Alterations in mitochondrial structure and function are early events of dexamethasone-induced thymocyte apoptosis
P. Petit (1995)
10.1126/science.7878463
Mechanisms and genes of cellular suicide
H. Steller (1995)
See more
Semantic Scholar Logo Some data provided by SemanticScholar