APRIL (protein)

{{Short description|Protein-coding gene in the species Homo sapiens}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox_gene}} '''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.<ref name="pmid9743536">{{cite journal | vauthors = 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 | title = APRIL, a new ligand of the tumor necrosis factor family, stimulates tumor cell growth | journal = The Journal of Experimental Medicine | volume = 188 | issue = 6 | pages = 1185–1190 | date = September 1998 | pmid = 9743536 | pmc = 2212534 | doi = 10.1084/jem.188.6.1185 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: TNFSF13 tumor necrosis factor (ligand) superfamily, member 13| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=8741|publisher=National Library of Medicine|date=10 October 2023|access-date=13 October 2023}}</ref> It is encoded by the ''TNFSF13'' gene.<ref name="entrez"/>

==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.<ref>{{cite journal | vauthors = 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 | title = APRIL-deficient mice have normal immune system development | journal = Molecular and Cellular Biology | volume = 24 | issue = 3 | pages = 997–1006 | date = February 2004 | pmid = 14729948 | pmc = 321448 | doi = 10.1128/MCB.24.3.997-1006.2004 }}</ref> However, APRIL-deficient mice have also been reported to possess a reduced ability to support plasma cell survival.<ref name="entrez2">{{cite journal | vauthors = Belnoue E, Pihlgren M, McGaha TL, Tougne C, Rochat AF, Bossen C, Schneider P, Huard B, Lambert PH, Siegrist CA | title = APRIL is critical for plasmablast survival in the bone marrow and poorly expressed by early-life bone marrow stromal cells | journal = Blood | volume = 111 | issue = 5 | pages = 2755–2764 | date = March 2008 | pmid = 18180376 | doi = 10.1182/blood-2007-09-110858 | doi-access = free }}</ref> 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.<ref>{{cite journal | vauthors = Roth W, Wagenknecht B, Klumpp A, Naumann U, Hahne M, Tschopp J, Weller M | title = APRIL, a new member of the tumor necrosis factor family, modulates death ligand-induced apoptosis | journal = Cell Death and Differentiation | volume = 8 | issue = 4 | pages = 403–410 | date = April 2001 | pmid = 11550092 | doi = 10.1038/sj.cdd.4400827 | doi-access = free }}</ref> Three alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported.

== Interactions ==

TNFSF13 has been shown to interact with TNFRSF13B<ref name="pmid10956646">{{cite journal | vauthors = 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 | title = Tumor necrosis factor (TNF) receptor superfamily member TACI is a high affinity receptor for TNF family members APRIL and BLyS | journal = The Journal of Biological Chemistry | volume = 275 | issue = 45 | pages = 35478–35485 | date = November 2000 | pmid = 10956646 | doi = 10.1074/jbc.M005224200 | doi-access = free }}</ref> and B-cell activating factor.<ref name="pmid12370363">{{cite journal | vauthors = Roschke V, Sosnovtseva S, Ward CD, Hong JS, Smith R, Albert V, Stohl W, Baker KP, Ullrich S, Nardelli B, Hilbert DM, Migone TS | title = BLyS and APRIL form biologically active heterotrimers that are expressed in patients with systemic immune-based rheumatic diseases | journal = Journal of Immunology | volume = 169 | issue = 8 | pages = 4314–4321 | date = October 2002 | pmid = 12370363 | doi = 10.4049/jimmunol.169.8.4314 | doi-access = free }}</ref>

== Clinical significance == APRIL is being explored as a target for autoimmune diseases and B cell malignancies.<ref>{{cite book | title = Therapeutic Targets of the TNF Superfamily | volume = 647 | vauthors = Ryan MC, Grewal IS | chapter = Targeting of BAFF and APRIL for Autoimmunity and Oncology | date=2009-01-01 | publisher = Springer | location = New York | isbn = 978-0-387-89519-2 | veditors = Grewal IS | series=Advances in Experimental Medicine and Biology | pages = 52–63 | doi = 10.1007/978-0-387-89520-8_4 |pmid = 19760066}}</ref> At least one anti-APRIL monoclonal antibody has been announced to enter phase I clinical trials for multiple myeloma.<ref>{{cite journal |date=April 2017|title=Development of a first in class APRIL fully blocking antibody BION-1301 for the treatment of multiple myeloma | url = http://www.abstractsonline.com/pp8/#!/4292/presentation/6077 | journal = AACR 2017 Proceedings }}</ref> {{clear}}

== References == {{reflist|33em}}

== Further reading == {{refbegin|33em}} * {{cite journal | vauthors = Bossen C, Schneider P | title = BAFF, APRIL and their receptors: structure, function and signaling | journal = Seminars in Immunology | volume = 18 | issue = 5 | pages = 263–275 | date = October 2006 | pmid = 16914324 | doi = 10.1016/j.smim.2006.04.006 | url = https://serval.unil.ch/notice/serval:BIB_89872BC6E950 }} * {{cite journal | vauthors = Tangye SG, Bryant VL, Cuss AK, Good KL | title = BAFF, APRIL and human B cell disorders | journal = Seminars in Immunology | volume = 18 | issue = 5 | pages = 305–317 | date = October 2006 | pmid = 16916610 | doi = 10.1016/j.smim.2006.04.004 }} * {{cite journal | vauthors = Treml LS, Crowley JE, Cancro MP | title = BLyS receptor signatures resolve homeostatically independent compartments among naïve and antigen-experienced B cells | journal = Seminars in Immunology | volume = 18 | issue = 5 | pages = 297–304 | date = October 2006 | pmid = 16919470 | doi = 10.1016/j.smim.2006.07.001 }} * {{cite journal | vauthors = Mackay F, Leung H | title = The role of the BAFF/APRIL system on T cell function | journal = Seminars in Immunology | volume = 18 | issue = 5 | pages = 284–289 | date = October 2006 | pmid = 16931039 | doi = 10.1016/j.smim.2006.04.005 }} * {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–174 | date = January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }} * {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–156 | date = October 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }} * {{cite journal | vauthors = Shu HB, Hu WH, Johnson H | title = TALL-1 is a novel member of the TNF family that is down-regulated by mitogens | journal = Journal of Leukocyte Biology | volume = 65 | issue = 5 | pages = 680–683 | date = May 1999 | pmid = 10331498 | doi = 10.1002/jlb.65.5.680 | s2cid = 1498303 | doi-access = free }} * {{cite journal | vauthors = Cousin P, Billotte J, Chaubert P, Shaw P | title = Physical map of 17p13 and the genes adjacent to p53 | journal = Genomics | volume = 63 | issue = 1 | pages = 60–68 | date = January 2000 | pmid = 10662545 | doi = 10.1006/geno.1999.6062 }} * {{cite journal | vauthors = Kelly K, Manos E, Jensen G, Nadauld L, Jones DA | title = APRIL/TRDL-1, a tumor necrosis factor-like ligand, stimulates cell death | journal = Cancer Research | volume = 60 | issue = 4 | pages = 1021–1027 | date = February 2000 | pmid = 10706119 }} * {{cite journal | vauthors = 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 | title = Tumor necrosis factor (TNF) receptor superfamily member TACI is a high affinity receptor for TNF family members APRIL and BLyS | journal = The Journal of Biological Chemistry | volume = 275 | issue = 45 | pages = 35478–35485 | date = November 2000 | pmid = 10956646 | doi = 10.1074/jbc.M005224200 | doi-access = free }} * {{cite journal | vauthors = 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 | title = APRIL and TALL-I and receptors BCMA and TACI: system for regulating humoral immunity | journal = Nature Immunology | volume = 1 | issue = 3 | pages = 252–256 | date = September 2000 | pmid = 10973284 | doi = 10.1038/79802 | s2cid = 6799584 }} * {{cite journal | vauthors = López-Fraga M, Fernández R, Albar JP, Hahne M | title = Biologically active APRIL is secreted following intracellular processing in the Golgi apparatus by furin convertase | journal = EMBO Reports | volume = 2 | issue = 10 | pages = 945–951 | date = October 2001 | pmid = 11571266 | pmc = 1084076 | doi = 10.1093/embo-reports/kve198 }} * {{cite journal | vauthors = 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 | title = APRIL modulates B and T cell immunity | journal = The Journal of Clinical Investigation | volume = 109 | issue = 12 | pages = 1587–1598 | date = June 2002 | pmid = 12070306 | pmc = 151011 | doi = 10.1172/JCI15034 }} * {{cite journal | vauthors = Roschke V, Sosnovtseva S, Ward CD, Hong JS, Smith R, Albert V, Stohl W, Baker KP, Ullrich S, Nardelli B, Hilbert DM, Migone TS | title = BLyS and APRIL form biologically active heterotrimers that are expressed in patients with systemic immune-based rheumatic diseases | journal = Journal of Immunology | volume = 169 | issue = 8 | pages = 4314–4321 | date = October 2002 | pmid = 12370363 | doi = 10.4049/jimmunol.169.8.4314 | doi-access = free }} * {{cite journal | vauthors = Pradet-Balade B, Medema JP, López-Fraga M, Lozano JC, Kolfschoten GM, Picard A, Martínez-A C, Garcia-Sanz JA, Hahne M | title = An endogenous hybrid mRNA encodes TWE-PRIL, a functional cell surface TWEAK-APRIL fusion protein | journal = The EMBO Journal | volume = 21 | issue = 21 | pages = 5711–5720 | date = November 2002 | pmid = 12411489 | pmc = 131062 | doi = 10.1093/emboj/cdf565 }} {{refend}}

== External links == * {{MeshName|TNFSF13+protein,+human}} * {{UCSC gene info|TNFSF13}}

Category:Clusters of differentiation