APRIL (protein) explained

A proliferation-inducing ligand (APRIL), also known as tumor necrosis factor ligand superfamily member 13 (TNFSF13), is a protein of the TNF superfamily recognized by the cell surface receptor TACI.^{[1] [2]} It is encoded by the TNFSF13 gene.^[2]

Nomenclature

In the cluster of differentiation terminology, APRIL is designated CD256.

Function

The protein encoded by this gene is a member of the tumor necrosis factor ligand (TNF) ligand family. This protein is a ligand for TNFRSF17/BCMA, a member of the TNF receptor family. This protein and its receptor are both found to be important for B cell development. In vivo experiments suggest an important role for APRIL in the long-term survival of plasma cells in the bone marrow. Mice deficient in APRIL have normal immune system development.^[3] However, APRIL-deficient mice have also been reported to possess a reduced ability to support plasma cell survival.^[4] In vitro experiments suggested that this protein may be able to induce apoptosis through its interaction with other TNF receptor family proteins such as TNFRSF6/FAS and TNFRSF14/HVEM.^[5] Three alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported.

Interactions

TNFSF13 has been shown to interact with TNFRSF13B^[6] and B-cell activating factor.^[7]

Clinical significance

APRIL is being explored as a target for autoimmune diseases and B cell malignancies.^[8] At least one anti-APRIL monoclonal antibody has been announced to enter phase I clinical trials for multiple myeloma.^[9]

Further reading

• Bossen C, Schneider P . BAFF, APRIL and their receptors: structure, function and signaling . Seminars in Immunology . 18 . 5 . 263–75 . October 2006 . 16914324 . 10.1016/j.smim.2006.04.006 .
• Tangye SG, Bryant VL, Cuss AK, Good KL . BAFF, APRIL and human B cell disorders . Seminars in Immunology . 18 . 5 . 305–17 . October 2006 . 16916610 . 10.1016/j.smim.2006.04.004 .
• Treml LS, Crowley JE, Cancro MP . BLyS receptor signatures resolve homeostatically independent compartments among naïve and antigen-experienced B cells . Seminars in Immunology . 18 . 5 . 297–304 . October 2006 . 16919470 . 10.1016/j.smim.2006.07.001 .
• Mackay F, Leung H . The role of the BAFF/APRIL system on T cell function . Seminars in Immunology . 18 . 5 . 284–9 . October 2006 . 16931039 . 10.1016/j.smim.2006.04.005 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Shu HB, Hu WH, Johnson H . TALL-1 is a novel member of the TNF family that is down-regulated by mitogens . Journal of Leukocyte Biology . 65 . 5 . 680–3 . May 1999 . 10331498 . 10.1002/jlb.65.5.680. 1498303 . free .
• Cousin P, Billotte J, Chaubert P, Shaw P . Physical map of 17p13 and the genes adjacent to p53 . Genomics . 63 . 1 . 60–8 . January 2000 . 10662545 . 10.1006/geno.1999.6062 .
• Kelly K, Manos E, Jensen G, Nadauld L, Jones DA . APRIL/TRDL-1, a tumor necrosis factor-like ligand, stimulates cell death . Cancer Research . 60 . 4 . 1021–7 . February 2000 . 10706119 .
• Wu Y, Bressette D, Carrell JA, Kaufman T, Feng P, Taylor K, Gan Y, Cho YH, Garcia AD, Gollatz E, Dimke D, LaFleur D, Migone TS, Nardelli B, Wei P, Ruben SM, Ullrich SJ, Olsen HS, Kanakaraj P, Moore PA, Baker KP . Tumor necrosis factor (TNF) receptor superfamily member TACI is a high affinity receptor for TNF family members APRIL and BLyS . The Journal of Biological Chemistry . 275 . 45 . 35478–85 . November 2000 . 10956646 . 10.1074/jbc.M005224200 . free .
• Yu G, Boone T, Delaney J, Hawkins N, Kelley M, Ramakrishnan M, McCabe S, Qiu WR, Kornuc M, Xia XZ, Guo J, Stolina M, Boyle WJ, Sarosi I, Hsu H, Senaldi G, Theill LE . APRIL and TALL-I and receptors BCMA and TACI: system for regulating humoral immunity . Nature Immunology . 1 . 3 . 252–6 . September 2000 . 10973284 . 10.1038/79802 . 6799584 .
• López-Fraga M, Fernández R, Albar JP, Hahne M . Biologically active APRIL is secreted following intracellular processing in the Golgi apparatus by furin convertase . EMBO Reports . 2 . 10 . 945–51 . October 2001 . 11571266 . 1084076 . 10.1093/embo-reports/kve198 .
• Stein JV, López-Fraga M, Elustondo FA, Carvalho-Pinto CE, Rodríguez D, Gómez-Caro R, De Jong J, Martínez-A C, Medema JP, Hahne M . APRIL modulates B and T cell immunity . The Journal of Clinical Investigation . 109 . 12 . 1587–98 . June 2002 . 12070306 . 151011 . 10.1172/JCI15034 .
• Litinskiy MB, Nardelli B, Hilbert DM, He B, Schaffer A, Casali P, Cerutti A . DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL . Nature Immunology . 3 . 9 . 822–9 . September 2002 . 12154359 . 10.1038/ni829 . 4621779 .
• Roschke V, Sosnovtseva S, Ward CD, Hong JS, Smith R, Albert V, Stohl W, Baker KP, Ullrich S, Nardelli B, Hilbert DM, Migone TS . BLyS and APRIL form biologically active heterotrimers that are expressed in patients with systemic immune-based rheumatic diseases . Journal of Immunology . 169 . 8 . 4314–21 . October 2002 . 12370363 . 10.4049/jimmunol.169.8.4314 . free .
• Pradet-Balade B, Medema JP, López-Fraga M, Lozano JC, Kolfschoten GM, Picard A, Martínez-A C, Garcia-Sanz JA, Hahne M . An endogenous hybrid mRNA encodes TWE-PRIL, a functional cell surface TWEAK-APRIL fusion protein . The EMBO Journal . 21 . 21 . 5711–20 . November 2002 . 12411489 . 131062 . 10.1093/emboj/cdf565 .

Notes and References

1. Hahne M, Kataoka T, Schröter M, Hofmann K, Irmler M, Bodmer JL, Schneider P, Bornand T, Holler N, French LE, Sordat B, Rimoldi D, Tschopp J . APRIL, a new ligand of the tumor necrosis factor family, stimulates tumor cell growth . The Journal of Experimental Medicine . 188 . 6 . 1185–90 . September 1998 . 9743536 . 2212534 . 10.1084/jem.188.6.1185 .
2. Web site: Entrez Gene: TNFSF13 tumor necrosis factor (ligand) superfamily, member 13. National Library of Medicine. 10 October 2023. 13 October 2023.
3. Varfolomeev E, Kischkel F, Martin F, Seshasayee D, Wang H, Lawrence D, Olsson C, Tom L, Erickson S, French D, Schow P, Grewal IS, Ashkenazi A . APRIL-deficient mice have normal immune system development . Molecular and Cellular Biology . 24 . 3 . 997–1006 . February 2004 . 14729948 . 321448 . 10.1128/MCB.24.3.997-1006.2004 .
4. Belnoue E, Pihlgren M, McGaha TL, Tougne C, Rochat AF, Bossen C, Schneider P, Huard B, Lambert PH, Siegrist CA . APRIL is critical for plasmablast survival in the bone marrow and poorly expressed by early-life bone marrow stromal cells . Blood . 111 . 5 . 2755–64 . March 2008 . 18180376 . 10.1182/blood-2007-09-110858 . free .
5. Roth W, Wagenknecht B, Klumpp A, Naumann U, Hahne M, Tschopp J, Weller M . APRIL, a new member of the tumor necrosis factor family, modulates death ligand-induced apoptosis . Cell Death and Differentiation . 8 . 4 . 403–10 . April 2001 . 11550092 . 10.1038/sj.cdd.4400827 . free .
6. Wu Y, Bressette D, Carrell JA, Kaufman T, Feng P, Taylor K, Gan Y, Cho YH, Garcia AD, Gollatz E, Dimke D, LaFleur D, Migone TS, Nardelli B, Wei P, Ruben SM, Ullrich SJ, Olsen HS, Kanakaraj P, Moore PA, Baker KP . Tumor necrosis factor (TNF) receptor superfamily member TACI is a high affinity receptor for TNF family members APRIL and BLyS . The Journal of Biological Chemistry . 275 . 45 . 35478–85 . November 2000 . 10956646 . 10.1074/jbc.M005224200 . free .
7. Roschke V, Sosnovtseva S, Ward CD, Hong JS, Smith R, Albert V, Stohl W, Baker KP, Ullrich S, Nardelli B, Hilbert DM, Migone TS . BLyS and APRIL form biologically active heterotrimers that are expressed in patients with systemic immune-based rheumatic diseases . Journal of Immunology . 169 . 8 . 4314–21 . October 2002 . 12370363 . 10.4049/jimmunol.169.8.4314 . free .
8. Book: Therapeutic Targets of the TNF Superfamily . 647 . Ryan . Maureen C. . Grewal . Iqbal S. . Targeting of BAFF and APRIL for Autoimmunity and Oncology . 2009-01-01 . Springer . New York . 978-0-387-89519-2 . Grewal . Iqbal S. . Advances in Experimental Medicine and Biology . 52–63 . 10.1007/978-0-387-89520-8_4 . 19760066.
9. April 2017. Development of a first in class APRIL fully blocking antibody BION-1301 for the treatment of multiple myeloma . AACR 2017 Proceedings .