The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
The DCC gene product induces apoptosis by a mechanism requiring receptor proteolysis
Open accessAbstract
The development of colonic carcinoma is associated with the mutation of a specific set of genes. One of these, DCC (deleted in colorectal cancer), is a candidate tumour-suppressor gene, and encodes a receptor for netrin-1, a molecule involved in axon guidance. Loss of DCC expression in tumours is not restricted to colon carcinoma, and, although there is no increase in the frequency of tumour formation in DCC hemizygous mice, reestablishment of DCC expression suppresses tumorigenicity. However, the mechanism of action of DCC is unknown. Here we show that DCC induces apoptosis in the absence of ligand binding, but blocks apoptosis when engaged by netrin-1. Furthermore, DCC is a caspase substrate, and mutation of the site at which caspase-3 cleaves DCC suppresses the pro-apoptotic effect of DCC completely. These results indicate that DCC may function as a tumour-suppressor protein by inducing apoptosis in settings in which ligand is unavailable (for example, during metastasis or tumour growth beyond local blood supply) through functional caspase cascades by a mechanism that requires cleavage of DCC at Asp 1,290.
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Cites
A Combinatorial Approach Defines Specificities of Members of the Caspase Family and Granzyme B
Thornberry, N. A., Rano, T. A., Peterson, E. P., Rasper, D. M., Timkey, T., Garcia-Calvo, M., Houtzager, V. M., Nordstrom, P. A., Roy, S., Vaillancourt, J. P., et al. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.29.17907 · Cited by 2,068
Identification of a Chromosome 18q Gene that Is Altered in Colorectal Cancers
Fearon, E. R., Cho, K. R., Nigro, J. M., Kern, S. E., Simons, J. W., Ruppert, J. M., Hamilton, Preisinger, A. C., Thomas, G., Kinzler, K. W., et al. (1990) · Science · doi:10.1126/science.2294591 · Cited by 1,739
Netrins are diffusible chemotropic factors for commissural axons in the embryonic spinal cord
Kennedy, T. E., Serafini, T., de la Torre, J., & Tessier-Lavigne, M. (1994) · Cell · doi:10.1016/0092-8674(94)90421-9 · Cited by 1,338
Netrin-1 Is Required for Commissural Axon Guidance in the Developing Vertebrate Nervous System
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Deleted in Colorectal Cancer (DCC) Encodes a Netrin Receptor
Keino-Masu, K., Masu, M., Hinck, L., Leonardo, E. D., Chan, S. S.-Y., Culotti, J. G., & Tessier-Lavigne, M. (1996) · Cell · doi:10.1016/s0092-8674(00)81336-7 · Cited by 1,013
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Induction of Apoptosis by the Low-Affinity NGF Receptor
Rabizadeh, S., Oh, J., Zhong, L.-T., Yang, J., Bitler, C. M., Butcher, L. L., & Bredesen, D. E. (1993) · Science · doi:10.1126/science.8332899 · Cited by 782
Self-citationPhenotype of mice lacking functional Deleted in colorectal cancer (Dec) gene
Fazeli, A., Dickinson, S. L., Hermiston, M. L., Tighe, R. V., Steen, R. G., Small, C. G., Stoeckli, E. T., Keino-Masu, K., Masu, M., Rayburn, H., et al. (1997) · Nature · doi:10.1038/386796a0 · Cited by 777
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Self-citationBiochemical Characteristics of Caspases-3, -6, -7, and -8
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Cited by
Mammalian Caspases: Structure, Activation, Substrates, and Functions During Apoptosis
Earnshaw, W. C., Martins, L. M., & Kaufmann, S. H. (1999) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.68.1.383 · Cited by 2,760
Anti-cancer activity of targeted pro-apoptotic peptides
Ellerby, H. M., Arap, W., Ellerby, L. M., Kain, R., Andrusiak, R., Rio, G. D., Krajewski, S., Lombardo, C. R., Rao, R., Ruoslahti, E., et al. (1999) · Nature Medicine · doi:10.1038/12469 · Cited by 936
Self-citationApoptosis of adherent cells by recruitment of caspase-8 to unligated integrins
Stupack, D. G., Puente, X. S., Boutsaboualoy, S., Storgard, C. M., & Cheresh, D. A. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.200106070 · Cited by 554
A second cytotoxic proteolytic peptide derived from amyloid β-protein precursor
Lu, D. C., Rabizadeh, S., Chandra, S., Shayya, R. F., Ellerby, L. M., Ye, X., Salvesen, G. S., Koo, E. H., & Bredesen, D. E. (2000) · Nature Medicine · doi:10.1038/74656 · Cited by 395
Self-citationApoptotic Pathway and MAPKs Differentially Regulate Chemotropic Responses of Retinal Growth Cones
Campbell, D. S., & Holt, C. E. (2003) · Neuron · doi:10.1016/s0896-6273(03)00158-2 · Cited by 303
Metadata
- Authors
- Mehlen, P., Rabizadeh, S., Snipas, S. J., Assa-Munt, N., Salvesen, G. S., & Bredesen, D. E.
- Venue
- Nature
- Published
- 1998-10
- Volume
- 395
- Issue
- 6704
- Pages
- 801-804
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1609447875
- Cited by
- 437
- References
- 25
- FWCI
- 6.08
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Mehlen, P., Rabizadeh, S., Snipas, S. J., Assa-Munt, N., Salvesen, G. S., & Bredesen, D. E. (1998). The DCC gene product induces apoptosis by a mechanism requiring receptor proteolysis. Nature. https://doi.org/10.1038/27441
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