Tumor Necrosis Factor Related Apoptosis Inducing Ligand
| Tumor Necrosis Factor Related Apoptosis Inducing Ligand | ||
|---|---|---|
| Properties of human protein | ||
| Mass / length primary structure | 281 amino acids | |
| Secondary to quaternary structure | Homotrimer, single-pass membrane protein | |
| Cofactor | Zn 2+ | |
| Identifier | ||
| Gene name | TNFSF10 | |
| External IDs | ||
T umor Necrosis Factor R elated A poptosis I nducing L igand ( TRAIL ) - (German: tumor necrosis factor-related apoptosis-inducing ligand) and for the immune system important protein. It is counted in the TNF / TNFR superfamily . Its task is to inactivate target cells by triggering apoptosis (programmed cell death) in the target cell.
Occurrence
It occurs as a secreted (released from the cell to the outside) or as a membrane-bound protein (anchored on the cell membrane), which is mostly formed by monocytes and B-lymphocytes . TRAIL is able to inactivate many different cell types in the body.
The protein is found in many tissues; it is concentrated in the lungs , spleen and prostate .
mechanism
In order to drive cells into apoptosis, it finds the DR4 or DR5 receptor (Death Cell Receptor) - also a protein - on the surface of its target cells. If TRAIL can bind to it, it activates caspase- 8 dependent apoptosis . This leads to the target cell killing itself and thus being inactivated.
TRAIL also presumably plays a role in the autophagocytosis of cells in the formation of tissues.
TRAIL and cancer
TRAIL is one of the most important factors in the inactivation of tumor cells. It influences the growth of tumor cells in vitro and in vivo ( model organism : house mouse ). TRAIL causes little damage to non-tumor cells. Treatment of healthy mice for 45 days with dissolved TRAIL did not cause cell damage. Because of these properties, it is currently being tested for its suitability as a therapeutic agent for cancer therapy.
TRAIL and pathogens
The apoptosis mechanism of TRAIL is used by some viruses and bacteria to regulate the T lymphocyte response against infected cells. They get cells to produce TRAIL. This kills T cells that would attack infected cells or bacteria. In this way, the pathogens sometimes escape the immune system. The influenza A / H5N1 , HI , herpes simplex , cytomegaly and measles virus have such mechanisms. In the case of bacteria, these include Staphylococcus aureus and Salmonella enterica Serovar Dublin.
TRAIL is believed to also play a role in liver necrosis caused by hepatitis by killing hepatocytes infected with the hepatitis virus.
literature
- Wiley SR, Schooley K, Smolak PJ, et al. : Identification and characterization of a new member of the TNF family that induces apoptosis . In: Immunity . 3, No. 6, December 1995, pp. 673-82. PMID 8777713 .
Web links
- Gillespie / reactome: TRAIL signaling
Individual evidence
- ↑ Mills KR, Reginato M, Debnath J, Queenan B, Brugge JS: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is required for induction of autophagy during lumen formation in vitro , PNAS 101: 3438-3443 (2004) PMID 14993595
- ↑ AM Chinnaiyan et al .: Combined effect of tumor necrosis factor-related apoptosis-inducing ligand and ionizing radiation in breast cancer therapy. In: PNAS 97, 2000, pp. 1754-1759. PMID 10677530
- ↑ Shi-Jun Zheng, Pu Wang, Galit Tsabary and Youhai H. Chen: Critical roles of TRAIL in hepatic cell death and hepatic inflammation , J Clin Invest 113: 58-64 (2004) doi : 10.1172 / JCI200419255