Neumeyer, Jens and Hallas, Cora and Merkel, Oliver and Winoto-Morbach, Supandi and Jakob, Marten and Thon, Lutz and Adam, Dieter and Schneider-Brachert, Wulf and Schuetze, Stefan (2006) TNF-receptor I defective in internalization allows for cell death through activation of neutral sphingomyelinase. EXPERIMENTAL CELL RESEARCH, 312 (11). pp. 2142-2153. ISSN 0014-4827, 1090-2422
Full text not available from this repository. (Request a copy)Abstract
The cytoplasmic tail of the tumor necrosis factor receptor I (TNF-RI) contains several functionally distinct domains involved in apoptotic signaling. Mutants of TNF-RI carrying deletions of the death domain (DD), internalization domain (TRID), and neutral sphingomyelinase domain (NSD), respectively, retransfected in cells devoid of TNF-RI and TNF-RII, constituted distinct tools to evaluate the specific role of each domain in downstream apoptotic signaling events. Deletion of DD abolishes activation of caspase-3 and -9 and apoptosis following treatment with TNF because of blocked assembly of the DISC. Nevertheless, TNF-RI Delta TRID, though lacking a DISC, still allows for residual activation of caspase-3 followed by cell death, although caspase-9 activation was not detected. This activity of caspase-3 is probably due to activation of neutral sphingomyelinase (N-SMase). Increased activity of this enzyme was detected in cells expressing TNF-RI ATRID following treatment with TNF, but not in any other cell line investigated. N-SMase is activated by factor associated with N-SMase (FAN). Because TNF-RI ATRID is retained at the cell surface, FAN may interact with the mutated receptor for a prolonged amount of time, thereby overactivating N-SMase. Double deletion of TRID and NSD abolished caspase-3 activation and apoptosis, confirming this hypothesis. (c) 2006 Elsevier Inc. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SIGNALING COMPLEX; CYTOCHROME-C; APOPTOSIS; PROTEASE; DOMAIN; MITOCHONDRIA; PROTEOLYSIS; FAS/APO-1; PATHWAYS; CERAMIDE; caspase; cathepsin D; sphingomyelinase; TNF-RI; apoptosis; DISC |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Feb 2021 11:26 |
| Last Modified: | 10 Feb 2021 11:26 |
| URI: | https://pred.uni-regensburg.de/id/eprint/34343 |
Actions (login required)
 |
View Item |
