General description

APRIL, a member of the TNF superfamily, is expressed in monocytes, macrophages, certain transformed cell lines, certain cancers of colon, and lymphoid tissues. APRIL, along with another TNF family member, BAFF, compete for two receptors, TACI and BCMA. ARPIL has the ability to stimulate proliferation of various tumor cell lines including Jurkat T cells and MCF-7 carcinoma cells. Like BAFF, APRIL also stimulates the proliferation of B and T cells. The human APRIL gene codes for at least four alternatively spliced transcriptional variants, which give rise to different isoforms of the APRIL precursor protein. All isoforms can be cleaved by the protease, furin, to release a soluble C-terminal fragment, which comprises the TNF like receptor binding of the APRIL precursor. Recombinant murine APRIL is a soluble 21.9 kDa protein, consisting of 192 amino acid residues.

Research area: Immunology and Cytokines

APRIL (a proliferation-inducing ligand) was identified in 1998 through database mining and is a member of the TNF (tumor necrosis factor) family. APRIL gene is localized to human chromosome 17p13, contains six exons, and is alternatively transcribed to 1.8, 2.1, and 2.4 kb mRNA transcripts. APRIL protein is composed of a cytosolic domain of 28 amino acids, and a transmembrane region. It also contains an exoplasmic region, made up of a stalk and a TNF domain. It shares the highest similarity to BLyS (B lymphocyte stimulator) protein, ~30% sequence similarity in the TNF domain. It is synthesized as a type II transmembrane protein and is proteolytically processed as a mature protein, which is a soluble and non-covalent trimer. Recombinant murine APRIL is a soluble 21.9 kDa protein, consisting of 192 amino acid residues.

Biochem/physiol Actions

A proliferation-inducing ligand (APRIL) and its ligand interaction activate several signaling pathways, including nuclear factor-kappa B (NF-κB), p38, c-Jun N-terminal kinase mitogen-activated protein kinase (JNK MAPK), and Protein Kinase B/Forkhead Box O (AKT/FOXO), which are necessary for promoting the survival and differentiation of B cells and plasma cells. Additionally, APRIL signaling aids in the regulation of cytokine production, the generation of humoral immunity, decreases T cell-dependent antibody responses, and facilitates IgA class switching. These functions highlight the crucial role of APRIL in regulating immune responses. Furthermore, APRIL is also known to induce immune cell apoptosis leading to immunosuppression, and tumor development.

Sequence

MRREVSRLQR SGGPSQKQGE RPWQSLWEQS PDVLEAWKDG AKSRRRRAVL TQKHKKKHSV LHLVPVNITS KDSDVTEVMW QPVLRRGRGL EAQGDIVRVW DTGIYLLYSQ VLFHDVTFTM GQVVSREGQG RRETLFRCIR SMPSDPDRAY NSCYSAGVFH LHQGDIITVK IPRANAKLSL SPHGTFLGFV KL

Physical form

Lyophilized from 10 mM Sodium Acetate, pH 5.0 + 100 mM Arginine.

Reconstitution

Centrifuge the vial prior to opening. Reconstitute in water to a concentration of 0.1-1.0 mg/ml. Do not vortex. This solution can be stored at 2-8Â°C for up to 1 week. For extended storage, it is recommended to further dilute in a buffer containing a carrier protein (example 0.1% BSA) and store in working aliquots at -20Â°C to -80Â°C.