The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
The Role of c-FLIP in Modulation of CD95-induced Apoptosis
Open accessAbstract
Upon stimulation, CD95 (APO-1/Fas) recruits the adapter molecule Fas-associated death domain protein (FADD)/MORT1 and caspase-8 (FADD-like interleukin-1beta-converting enzyme (FLICE)/MACH/MCH5) into the death-inducing signaling complex (DISC). Recently, a molecule with sequence homology to caspase-8 was identified, termed cellular FLICE-inhibitory protein (c-FLIP). c-FLIP has been controversially reported to possess apoptosis-promoting and -inhibiting functions. Using c-FLIP-specific monoclonal antibodies, we now show that c-FLIP is expressed in two isoforms, both of which, like FADD and caspase-8, are recruited to the CD95 DISC in a stimulation-dependent fashion. In stably transfected BJAB cells, c-FLIP blocks caspase-8 activation at the DISC and thereby inhibits CD95-mediated apoptosis. During this process, both caspase-8 and c-FLIP undergo cleavage between the p18 and p10 subunits, generating two stable intermediates of 43 kDa that stay bound to the DISC. c-FLIP has been suggested to play a role in protecting activated peripheral T cells from CD95-mediated apoptosis (Irmler, M., Thome, M., Hahne, M., Schneider, P., Hofmann, K., Steiner, V., Bodmer, J. L. , Schroter, M., Burns, K., Mattmann, C., Rimoldi, D., French, L. E., and Tschopp, J. (1997) Nature 388, 190-195). In contrast to this hypothesis, neither caspase-8 nor c-FLIP were cleaved in these cells, ruling out c-FLIP as the main factor regulating DISC activity. Moreover, recruitment of FADD, caspase-8, and c-FLIP to the DISC was strongly reduced in the apoptosis-resistant but readily detectable in the apoptosis-sensitive T cells.
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Self-citationTwo CD95 (APO‐1/Fas) signaling pathways
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Self-citationInhibition of death receptor signals by cellular FLIP
Irmler, M., Thome, M., Hahne, M., Schneider, P., Hofmann, K., Steiner, V., Bodmer, J.-L., Schröter, M., Burns, K., Mattmann, C., et al. (1997) · Nature · doi:10.1038/40657 · Cited by 2,563
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Self-citationHsu, H., Shu, H.-B., Pan, M.-G., & Goeddel, D. V. (1996) · Cell · doi:10.1016/s0092-8674(00)80984-8 · Cited by 1,998
Monoclonal Antibody-Mediated Tumor Regression by Induction of Apoptosis
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Self-citationAutocrine T-cell suicide mediated by APO-1/(Fas/CD95)
Dhein, J., Walczak, H., Bäumler, C., Debatin, K.-M., & Krammer, P. H. (1995) · Nature · doi:10.1038/373438a0 · Cited by 1,609
Self-citationFas(CD95)/FasL interactions required for programmed cell death after T-cell activation
Ju, S.-T., Panka, D. J., Cui, H., Ettinger, R., EI-Khatib, M., Sherr, D. H., Stanger, B. Z., & Marshak-Rothstein, A. (1995) · Nature · doi:10.1038/373444a0 · Cited by 1,499
Cited by
Apoptosis: A Review of Programmed Cell Death
Elmore, S. (2007) · Toxicologic Pathology · doi:10.1080/01926230701320337 · Cited by 13,853
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680
Self-citationApo2L/TRAIL-Dependent Recruitment of Endogenous FADD and Caspase-8 to Death Receptors 4 and 5
Kischkel, F. C., Lawrence, D. A., Chuntharapai, A., Schow, P., Kim, K. J., & Ashkenazi, A. (2000) · Immunity · doi:10.1016/s1074-7613(00)80212-5 · Cited by 975
The Long Form of FLIP Is an Activator of Caspase-8 at the Fas Death-inducing Signaling Complex
Micheau, O., Thome, M., Schneider, P., Holler, N., Tschopp, J., Nicholson, D. W., Briand, C., & Grütter, M. G. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206882200 · Cited by 482
Apoptosis, necrosis and necroptosis: cell death regulation in the intestinal epithelium
Günther, C., Neumann, H., Neurath, M. F., & Becker, C. (2013) · Gut · doi:10.1136/gutjnl-2011-301364 · Cited by 462
Metadata
- Authors
- Scaffidi, C., Schmitz, I., Krammer, P. H., & Peter, M. E.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-01
- Volume
- 274
- Issue
- 3
- Pages
- 1541-1548
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1975155851
- Cited by
- 819
- References
- 49
- FWCI
- 18.27
- Type
- journal article
- Language
- en
- Open access
- hybrid
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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