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| Death receptor recruitment of endogenous caspase-10 and apoptosis initiation in the absence of caspase-8. |
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| Author(s): Kischkel FC, Lawrence DA, Tinel A, LeBlanc H, Virmani A, Schow P, Gazdar A, Blenis J, Arnott D, Ashkenazi A |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 276 Issue: 49 Pages: 46639-46646 Published: DEC 7 2001 |
| Times Cited: 234 References: 43 |
| Abstract: Caspase-8 is believed to play an obligatory role in apoptosis initiation by death receptors, but the role of its structural relative, caspase-10, remains controversial. Although earlier evidence implicated caspase-10 in apoptosis signaling by CD95L and Apo2L/TRAIL, recent studies indicated that these death receptor ligands recruit caspase-8 but not caspase-10 to their death-inducing signaling complex (DISC) even in presence of abundant caspase-10. We characterized a series of caspase-10-specific antibodies and found that certain commercially available antibodies cross-react with HSP60, shedding new light on previous results. The majority of 55 lung and breast carcinoma cell lines expressed mRNA for both caspase-8 and -10; however, immunoblot analysis revealed that caspase-10 protein expression was more frequently absent than that of caspase-8, suggesting a possible selective pressure against caspase-10 production in cancer cells. In nontransfected cells expressing both caspases, CD95L and Apo2L/TRAIL recruited endogenous caspase-10 as well as caspase-8 to their DISC, where both enzymes were proteolytically processed with similar kinetics. Caspase-10 recruitment required the adaptor FADD/ Mort1, and caspase-10 cleavage in vitro required DISC assembly, consistent with the processing of an apoptosis initiator. Cells expressing only one of the caspases underwent ligand-induced apoptosis, indicating that each caspase can initiate apoptosis independently of the other. Thus, apoptosis signaling by death receptors involves not only caspase-8 but also caspase-10, and both caspases may have equally important roles in apoptosis initiation. |
| Document Type: Article |
| Language: English |
| Reprint Address: Ashkenazi, A (reprint author), Genentech Inc, Dept Mol Oncol, 1 DNA Way, S San Francisco, CA 94080 USA |
Addresses:
1. Genentech Inc, Dept Mol Oncol, S San Francisco, CA 94080 USA
2. Genentech Inc, Dept Cell Biol, S San Francisco, CA 94080 USA
3. Genentech Inc, Dept Prot Chem, S San Francisco, CA 94080 USA
4. Univ Texas, SW Med Sch, Dallas, TX 75390 USA
5. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: 499LR |
| ISSN: 0021-9258 |
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