| Tumor necrosis factor(TNF), FasL, TRAIL are all apoptosis related factors of TNF family. They can bind to their specific receptors and induce the death of tumor cells and non transformed cells, therefore ,play a pivotal roles in the tumor inhibition , immune system stabilization and disease pathogenesis. Here we describe a new ligand in this family, designated TWEAK( Tumor necrosis factor-like weak inducer of apoptosis, TWEAK), the cDNA is 1.3kb, first cloned by Chiceportiche in 1997, and named as TNF ligand superfamily member 12 .It is located on chromosome 17p13. The amino terminal of human and murine both contain the ATTAAA sequence. It is a typeâ…¡membrane protein with 249 aa, the MW is 27kDa with expression in a wide range of tissue and cells. The mouse and human versions of this protein are unusually conserved with 93% amino acid identity in the receptor binding domains. Human TWEAK shares 79%, 75%, 86%, and 75% homology with TNF, TRAIL, FASL, and CD40L respectively. The spanning membrane domain connects the receptor binding domain with a stem structure, which are rich of basic amino acids and sensitive to protein hydrolysis. The 139 aa is glycosylated. Marsters found a new cDNA in human embryonic kidney library , named Apo3L and the product is the same as TWEAK , but unlike other TNF family members, it is expressed in many normal tissue as the ligand with various biological activity, including apoptosis induction, inflammation participation, immune regulation, and vascular endothelial cell formation and angiogenesis. |