APRIL (Fc-Fusion)

APRIL interacts with BCMA and TACI. It plays a role in B cell development through its interaction with BCMA. It is also known to express at high levels in transformed cells and some tumors. Biology of APRIL-TACI axis is less known. Interestingly, APRIL is capable of forming heteromers with a closed related TNFSF member, BAFF. The heteromers are known to be associated with inflammatory autoimmune disorders.

Interacting protein(s): BCMA (P7011F), TACI (P7012F)
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Quick Spec

Description

APRIL (proliferation-inducing ligand) is expressed a type II membrane protein member of the TNF superfamily. APRIL is present as the membrane-anchored protein or as a proteolytically processed soluble form. APRIL and BAFF, another TNF superfamily member, share two receptors, BCMA (B cell maturation) and TACI (transmembrane activator and calcium-modulating cyclophilin ligand interactor).

BCMA has a higher affinity for APRIL than BAFF, yet TACI binds both APRIL and BAFF equally well. The extracellular domain of APRIL contains a beta jelly roll structure and is responsible for the trimerization of APRIL. Binding of receptor molecules at the clefts between trimeric subunits brings the intracellular domains of the receptor proteins to proximity and triggers the signalling events.

APRIL is known for two key biological functions: (1) long term survival of plasma cells and (2) tumour growth both in the in vivo and in vitro settings.

Amino Acid Sequence

References

1. Hahne M, Kataoka T, Schroter M, Hofmann K, Irmler M, Bodmer JL, et al. (1998). APRIL, a New Ligand of the Tumor Necrosis Factor Family, Stimulates Tumor Cell Growth. J Exp Med 188: 1185–1190.
2. Wu Y, Bressette D, Carrell JA, Kaufman T, Feng P, et al. (2000). Tumor necrosis factor (TNF) receptor superfamily member TACI is a high affinity receptor for TNF family members APRIL and BLyS. J. Biol. Chem. 275: 35478–35485.
3. Roschke V, Sosnovtseva S, Ward CD, Hong JS, Smith R, et al. (2002). BLyS and APRIL form biologically active heterotrimers that are expressed in patients with systemic immune-based rheumatic diseases. J. Immunol. 169: 4314–4321
4. Benson MJ, Dillon SR, Castigli E, Geha RS, Xu S, Lam KP, Noelle RJ (2008) The dependence of plasma cells and independence of memory B cells on BAFF and APRIL. J Immunol. 180:3655-3659.