Fig. 1.

Biology of transmembrane TNF-α and soluble TNF-α.

Transmembrane TNF-α is a precursor form of soluble TNF-α that is expressed on TNF-α-producing cells as a homotrimer. After processing by TACE, soluble TNF-α is generated and binds to TNF-R1 or -R2. Transmembrane TNF-α also binds to TNF-R1 and -R2. Upon binding to TNF receptors, both transmembrane and soluble TNF-α mediate pleiotropic effects (apoptosis, cell proliferation and cytokine production). The remaining transmembrane TNF-α after cleavage with TACE is further processed by SPPL2b and the intracellular domain is translocated into the nucleus and is supposed to mediate cytokine production. tmTNF: transmembrane TNF-α; sTNF: soluble TNF-α.