Genomes and Genes
Gene Symbol: ced-3
Description: Cell death protein 3 subunit p17;hypothetical protein
Alias: Cell death protein 3 subunit p17;hypothetical protein
Species: Caenorhabditis elegans
- Shaham S. Identification of multiple Caenorhabditis elegans caspases and their potential roles in proteolytic cascades. J Biol Chem. 1998;273:35109-17 pubmed..These results suggest that C. elegans encodes several caspases that might act in proteolytic cascades to regulate processes such as programmed cell death. ..
- Chan S, Yee K, Tan K, Yu V. The Caenorhabditis elegans sex determination protein FEM-1 is a CED-3 substrate that associates with CED-4 and mediates apoptosis in mammalian cells. J Biol Chem. 2000;275:17925-8 pubmed..Similarly, Apaf-1, the mammalian homologue of CED-4 was found to associate with F1Aalpha. These data suggest that FEM-1 and F1Aalpha may mediate apoptosis by communicating directly with the core machinery of apoptosis. ..
- Nakagawa A, Shi Y, Kage Nakadai E, Mitani S, Xue D. Caspase-dependent conversion of Dicer ribonuclease into a death-promoting deoxyribonuclease. Science. 2010;328:327-34 pubmed publisher..DCR-1 functions in fragmenting chromosomal DNA during apoptosis, in addition to processing of small RNAs, and undergoes a protease-mediated conversion from a ribonuclease to a deoxyribonuclease. ..
- Qi S, Pang Y, Hu Q, Liu Q, Li H, Zhou Y, et al. Crystal structure of the Caenorhabditis elegans apoptosome reveals an octameric assembly of CED-4. Cell. 2010;141:446-57 pubmed publisher..The structure of the CED-4 apoptosome reveals shared principles for the NB-ARC family of AAA(+) ATPases and suggests a mechanism for the activation of CED-3. ..
- Chinnaiyan A, O Rourke K, Lane B, Dixit V. Interaction of CED-4 with CED-3 and CED-9: a molecular framework for cell death. Science. 1997;275:1122-6 pubmed..Thus, CED-4 plays a central role in the cell death pathway, biochemically linking CED-9 and the Bcl-2 family to CED-3 and the ICE family of pro-apoptotic cysteine proteases. ..
- Reddien P, Andersen E, Huang M, Horvitz H. DPL-1 DP, LIN-35 Rb and EFL-1 E2F act with the MCD-1 zinc-finger protein to promote programmed cell death in Caenorhabditis elegans. Genetics. 2007;175:1719-33 pubmed..We propose that the DPL-1 DP, MCD-1 zinc finger, EFL-1 E2F, LIN-35 Rb, LIN-37 Mip40, and LIN-52 dLin52 proteins act together in transcriptional regulation to promote programmed cell death. ..
- Denning D, Hatch V, Horvitz H. Programmed elimination of cells by caspase-independent cell extrusion in C. elegans. Nature. 2012;488:226-30 pubmed publisher..Our findings reveal a mechanism for apoptotic cell elimination that is fundamentally distinct from that of canonical programmed cell death. ..
- Geng X, Shi Y, Nakagawa A, Yoshina S, Mitani S, Shi Y, et al. Inhibition of CED-3 zymogen activation and apoptosis in Caenorhabditis elegans by caspase homolog CSP-3. Nat Struct Mol Biol. 2008;15:1094-101 pubmed publisher..However, CSP-3 does not block CED-3 activation induced by CED-4, nor does it inhibit the activity of the activated CED-3 protease. Therefore CSP-3 uses a previously unreported mechanism to protect cells from apoptosis. ..
- Yuan J, Shaham S, Ledoux S, Ellis H, Horvitz H. The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme. Cell. 1993;75:641-52 pubmed..We propose that the CED-3 protein acts as a cysteine protease in the initiation of programmed cell death in C. elegans and that cysteine proteases also function in programmed cell death in mammals. ..
- Kinchen J, Cabello J, Klingele D, Wong K, Feichtinger R, Schnabel H, et al. Two pathways converge at CED-10 to mediate actin rearrangement and corpse removal in C. elegans. Nature. 2005;434:93-9 pubmed
- Wu D, Wallen H, Inohara N, Nunez G. Interaction and regulation of the Caenorhabditis elegans death protease CED-3 by CED-4 and CED-9. J Biol Chem. 1997;272:21449-54 pubmed..Thus, these results provide evidence that CED-4 and CED-9 regulate the activity of CED-3 through physical interactions, which may provide a molecular basis for the control of programmed cell death in C. elegans. ..
- Conradt B, Horvitz H. The C. elegans protein EGL-1 is required for programmed cell death and interacts with the Bcl-2-like protein CED-9. Cell. 1998;93:519-29 pubmed..We propose that EGL-1 activates programmed cell death by binding to and directly inhibiting the activity of CED-9, perhaps by releasing the cell death activator CED-4 from a CED-9/CED-4-containing protein complex. ..
- Brantley S, Cotten S, Lamson D, Smith G, Liu R, Williams K. Discovery of small molecule inhibitors for the C. elegans caspase CED-3 by high-throughput screening. Biochem Biophys Res Commun. 2017;491:773-779 pubmed publisher..From these, four distinct chemotypes were identified. The inhibitor scaffolds described here could lead to the development of selective molecular probes to facilitate our understanding of programmed cell death in this model organism. ..
- Brady G, Duckett C. A caspase homolog keeps CED-3 in check. Trends Biochem Sci. 2009;34:104-7 pubmed publisher..Now, a new study identifies CSP-3 as an important negative regulator of CED-3 during C. elegans development. ..
- Contreras V, Friday A, Morrison J, Hao E, Keiper B. Cap-independent translation promotes C. elegans germ cell apoptosis through Apaf-1/CED-4 in a caspase-dependent mechanism. PLoS ONE. 2011;6:e24444 pubmed publisher..These findings support a new paradigm in which modal changes in protein synthesis act as a physiological signal to initiate cell death, rather than occur merely as downstream consequences of the apoptotic event. ..
- Cizeau J, Ray R, Chen G, Gietz R, Greenberg A. The C. elegans orthologue ceBNIP3 interacts with CED-9 and CED-3 but kills through a BH3- and caspase-independent mechanism. Oncogene. 2000;19:5453-63 pubmed..ceBNIP3 kills mammalian cells by a caspase-independent mechanism. In conclusion, we find that although ceBNIP3 interacts with CED-9 and CED-3 it kills by a BH3- and caspase-independent mechanism. ..
- Yuan J, Horvitz H. A first insight into the molecular mechanisms of apoptosis. Cell. 2004;116:S53-6, 1 p following S59 pubmed
- Chen X, Wang Y, Chen Y, Harry B, Nakagawa A, Lee E, et al. Regulation of CED-3 caspase localization and activation by C. elegans nuclear-membrane protein NPP-14. Nat Struct Mol Biol. 2016;23:958-964 pubmed publisher..Our results reveal a critical role of nuclei and nuclear-membrane proteins in regulating the activation and localization of CED-3. ..
- Huang C, Chen J, Wu S, Tan C, Tzeng R, Lu P, et al. C. elegans EIF-3.K promotes programmed cell death through CED-3 caspase. PLoS ONE. 2012;7:e36584 pubmed publisher..K. Because human eIF3k was able to partially substitute for C. elegans eif-3.K in the promotion of cell death, this WH domain-dependent EIF-3.K-mediated cell death process has potentially been conserved throughout evolution. ..
- Irmler M, Hofmann K, Vaux D, Tschopp J. Direct physical interaction between the Caenorhabditis elegans 'death proteins' CED-3 and CED-4. FEBS Lett. 1997;406:189-90 pubmed..Similarly, CED-4 was found to interact with CED-3. Thus, the activity of the death protease CED-3 appears to be controlled by CED-4 through a direct physical interaction. ..
- Nehme R, Grote P, Tomasi T, Loser S, Holzkamp H, Schnabel R, et al. Transcriptional upregulation of both egl-1 BH3-only and ced-3 caspase is required for the death of the male-specific CEM neurons. Cell Death Differ. 2010;17:1266-76 pubmed publisher..Finally, we present evidence that the timing of the death of the CEMs is controlled by TRA-1 Gli, the terminal global regulator of somatic sexual fate in C. elegans. ..
- Conradt B, Wu Y, Xue D. Programmed Cell Death During Caenorhabditis elegans Development. Genetics. 2016;203:1533-62 pubmed publisher..Further studies of programmed cell death in C. elegans will continue to advance our understanding of how programmed cell death is regulated, activated, and executed in general. ..
- Meng L, Mulcahy B, Cook S, Neubauer M, Wan A, Jin Y, et al. The Cell Death Pathway Regulates Synapse Elimination through Cleavage of Gelsolin in Caenorhabditis elegans Neurons. Cell Rep. 2015;11:1737-48 pubmed publisher..Our data suggest that activation of the CED pathway contributes to selective elimination of synapses through disassembly of the actin filament network. ..
- Weaver B, Zabinsky R, Weaver Y, Lee E, Xue D, Han M. CED-3 caspase acts with miRNAs to regulate non-apoptotic gene expression dynamics for robust development in C. elegans. elife. 2014;3:e04265 pubmed publisher..This mechanism may critically contribute to the robustness of gene expression dynamics governing proper developmental control. ..
- Chen Y, Mapes J, Lee E, Skeen Gaar R, Xue D. Caspase-mediated activation of Caenorhabditis elegans CED-8 promotes apoptosis and phosphatidylserine externalization. Nat Commun. 2013;4:2726 pubmed publisher..elegans. Our finding identifies a crucial link between caspase activation and PS externalization, which triggers phagocytosis of apoptotic cells. ..
- Weaver B, Weaver Y, Mitani S, Han M. Coupled Caspase and N-End Rule Ligase Activities Allow Recognition and Degradation of Pluripotency Factor LIN-28 during Non-Apoptotic Development. Dev Cell. 2017;41:665-673.e6 pubmed publisher..The interdependence of these proteolytic activities provides a paradigm for non-apoptotic caspase-mediated protein inactivation. ..
- Jaramillo Lambert A, Harigaya Y, Vitt J, Villeneuve A, Engebrecht J. Meiotic errors activate checkpoints that improve gamete quality without triggering apoptosis in male germ cells. Curr Biol. 2010;20:2078-89 pubmed publisher..We propose that the recombination checkpoint functions in male germ cells to promote repair of meiotic recombination intermediates, thereby improving the fidelity of chromosome transmission in the absence of apoptosis. ..
- Yasuda M, D Sa Eipper C, Gong X, Chinnadurai G. Regulation of apoptosis by a Caenorhabditis elegans BNIP3 homolog. Oncogene. 1998;17:2525-30 pubmed..Our results suggest that ceBNIP3 may be a novel component of the C. elegans apoptosis paradigm and may initiate apoptosis by recruiting CED-3 to mitochondria and other cytoplasmic membranes. ..
- Koseki T, Inohara N, Chen S, Nunez G. ARC, an inhibitor of apoptosis expressed in skeletal muscle and heart that interacts selectively with caspases. Proc Natl Acad Sci U S A. 1998;95:5156-60 pubmed..Delivery of ARC by gene transfer or enhancement of its endogenous activity may provide a strategy for the treatment of diseases that are characterized by inappropriately increased cell death in muscle tissue. ..
- Parrish J, Yang C, Shen B, Xue D. CRN-1, a Caenorhabditis elegans FEN-1 homologue, cooperates with CPS-6/EndoG to promote apoptotic DNA degradation. EMBO J. 2003;22:3451-60 pubmed..Our results suggest that CRN-1/FEN-1 may play a critical role in switching the state of cells from DNA replication/repair to DNA degradation during apoptosis. ..
- Chaudhary D, O Rourke K, Chinnaiyan A, Dixit V. The death inhibitory molecules CED-9 and CED-4L use a common mechanism to inhibit the CED-3 death protease. J Biol Chem. 1998;273:17708-12 pubmed..These results provide a simple mechanism for how CED-9 functions to block CED-4-mediated CED-3 processing and cell death. ..
- Yan N, Xu Y, Shi Y. 2:1 Stoichiometry of the CED-4-CED-9 complex and the tetrameric CED-4: insights into the regulation of CED-3 activation. Cell Cycle. 2006;5:31-4 pubmed..On the basis of structural and biochemical analyses, working models are proposed to explain the mechanism by which CED-4 facilitates CED-3 activation. ..
- Neukomm L, Nicot A, Kinchen J, Almendinger J, Pinto S, Zeng S, et al. The phosphoinositide phosphatase MTM-1 regulates apoptotic cell corpse clearance through CED-5-CED-12 in C. elegans. Development. 2011;138:2003-14 pubmed publisher..Finally, we show that the CED-12 PH domain can bind to PtdIns(3,5)P(2) (one target of MTM-1 phosphatase activity), suggesting that MTM-1 might regulate CED-12 recruitment to the plasma membrane. ..
- Duan H, Dixit V. RAIDD is a new 'death' adaptor molecule. Nature. 1997;385:86-9 pubmed..Finally, alternations in the sequence of the N-terminal domain that are equivalent to inactivating mutations in the C. elegans ced-3 gene prevent homophilic binding, highlighting the potentially primordial nature of this interaction. ..
- Nakagawa A, Sullivan K, Xue D. Caspase-activated phosphoinositide binding by CNT-1 promotes apoptosis by inhibiting the AKT pathway. Nat Struct Mol Biol. 2014;21:1082-90 pubmed publisher..Our findings reveal a new mechanism that negatively regulates AKT cell signaling to promote apoptosis and that may restrict cell growth and proliferation in normal cells. ..
- Joshi P, Eisenmann D. The Caenorhabditis elegans pvl-5 gene protects hypodermal cells from ced-3-dependent, ced-4-independent cell death. Genetics. 2004;167:673-85 pubmed..elegans. This suggests that loss of pvl-5 function leads to the activation of a ced-3-dependent, ced-4-independent form of PCD and that pvl-5 may normally function to protect cells from inappropriate activation of the apoptotic pathway. ..
- Chinnaiyan A, Chaudhary D, O Rourke K, Koonin E, Dixit V. Role of CED-4 in the activation of CED-3. Nature. 1997;388:728-9 pubmed
- Tzur Y, Margalit A, Melamed Book N, Gruenbaum Y. Matefin/SUN-1 is a nuclear envelope receptor for CED-4 during Caenorhabditis elegans apoptosis. Proc Natl Acad Sci U S A. 2006;103:13397-402 pubmed..The finding that matefin/SUN-1 is required for the execution of apoptosis adds an important link between cytoplasmic and nuclear apoptotic events. ..
- Denning D, Hatch V, Horvitz H. Both the caspase CSP-1 and a caspase-independent pathway promote programmed cell death in parallel to the canonical pathway for apoptosis in Caenorhabditis elegans. PLoS Genet. 2013;9:e1003341 pubmed publisher..We conclude that both caspase-dependent and caspase-independent pathways promote apoptotic programmed cell death and the phagocytosis of cell corpses in parallel to the canonical apoptosis pathway involving CED-3 activation. ..
- Huang W, Jiang T, Choi W, Qi S, Pang Y, Hu Q, et al. Mechanistic insights into CED-4-mediated activation of CED-3. Genes Dev. 2013;27:2039-48 pubmed publisher..The mechanism of CED-3 activation represents a major revision of the prevailing model for initiator caspase activation. ..
- Liu W, Lin Y, Wang J, Liou W, Hou R, Wu Y, et al. Restriction of vaccinia virus replication by a ced-3 and ced-4-dependent pathway in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2006;103:4174-9 pubmed..Therefore, the core PCD genes possess a unique function in controlling vaccinia virus replication in C. elegans. ..
- Hugunin M, Quintal L, Mankovich J, Ghayur T. Protease activity of in vitro transcribed and translated Caenorhabditis elegans cell death gene (ced-3) product. J Biol Chem. 1996;271:3517-22 pubmed
- Park D, Jia H, Rajakumar V, Chamberlin H. Pax2/5/8 proteins promote cell survival in C. elegans. Development. 2006;133:4193-202 pubmed..elegans bcl-2 gene. These results identify a mechanism for Pax2/5/8-mediated regulation of cell death, and underscore the importance of transcriptional regulation of core apoptotic pathway genes in influencing cell survival. ..
- Westein S, Scott F, Hawkins C. Analysis of the minimal specificity of CED-3 using a yeast transcriptional reporter system. Biochim Biophys Acta. 2008;1783:448-54 pubmed..Apart from an absolute requirement for aspartate at the P1 position, CED-3 is a relatively promiscuous caspase capable of cleaving substrates bearing many amino acids at P4-P2 sites. ..
- Erdélyi P, Borsos E, Takacs Vellai K, Kovacs T, Kovacs A, Sigmond T, et al. Shared developmental roles and transcriptional control of autophagy and apoptosis in Caenorhabditis elegans. J Cell Sci. 2011;124:1510-8 pubmed publisher..The identification of apoptosis and autophagy as compensatory cellular pathways in C. elegans might help us to understand how dysregulated PCD in humans can lead to diverse pathologies, including cancer, neurodegeneration and diabetes. ..