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Cutting Edge: A Dominant Negative Form of TNF-α Converting Enzyme Inhibits ProTNF and TNFRII Secretion
| Content Provider | Scilit |
|---|---|
| Author | Solomon, Kimberly A. Pesti, Nancy Wu, Guoxin Newton, Robert C. |
| Copyright Year | 1999 |
| Description | TNF-α converting enzyme (TACE) is the protease responsible for processing proTNF from the 26-kDa membrane-anchored precursor to the secreted 17-kDa TNF-α. We show here that a deletion mutant of TACE (dTACE), lacking the pro and catalytic domains of the protease, acts as a dominant negative for proTNF processing in transfected HEK293 cells. We used the same system to test the effect of dTACE on TNFRII processing. Overexpression of dTACE with TNFRII resulted in >80% inhibition of TNFRII shedding. Although significant inhibition of TNF-α and TNFRII shedding was achieved with dTACE, we could not detect a cell surface accumulation of the noncleaved substrates above that observed in the absence of dTACE. Our results suggest that TNFRII is a substrate for TACE, and that dTACE is capable of interfering with the function of endogenous TACE, either by binding and sequestering TACE substrates via the disintegrin domain, transmembrane domain, or cytoplasmic tail, or by some other mechanism that has yet to be determined. |
| Ending Page | 4108 |
| Page Count | 4 |
| Starting Page | 4105 |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.163.8.4105 |
| Journal | The Journal of Immunology |
| Issue Number | 8 |
| Volume Number | 163 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 1999-10-15 |
| Access Restriction | Open |
| Subject Keyword | Cell Biology Tnf Α |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
