Description
APRIL (a proliferation-inducing ligand), also known as TNFSF13, TALL2, TRDL1, and CD256, is a member of the TNF ligand superfamily. It is synthesized as a 32 kDa proprotein which is cleaved by furin in the Golgi to release the active 17 kDa soluble molecule. Secreted human APRIL, which consists almost entirely of a single TNF homology domain, shares 85% amino acid sequence identity with mouse and rat APRIL. Both APRIL and its close relative BAFF bind and signal through the TNF superfamily receptors TACI and BCMA, while BAFF additionally functions through BAFF R. APRIL binds to heparan sulfate proteoglycans (HSPGs) independently of its binding to TACI and BCMA. The interaction with HSPGs induces APRIL oligomerization, and this augments TACI-, or BMCA-mediated effects. HSPGs are also critical for the tumor growth-promoting effects attributed to APRIL. APRIL can form bioactive heterotrimers with BAFF, and these circulate in the serum of patients with rheumatic immune disorders. TWE-PRIL is a bioactive hybrid protein produced by gene splicing. It consists of the intracellular domain, transmembrane segment, and stalk region of TWEAK fused to the TNF homology domain of APRIL. TWE-PRIL is expressed in monocytes and activated T cells and, in contrast to APRIL, is presented on the cell surface. APRIL enhances the proliferation and survival of plasma cells and also promotes T cell-dependent humoral responses.