APRIL (protein)

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.[5][6] It is encoded by the TNFSF13 gene.[6]

TNFSF13
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTNFSF13, APRIL, CD256, TALL-2, TALL2, TRDL-1, ZTNF2, UNQ383/PRO715, TNLG7B, tumor necrosis factor superfamily member 13, TNF superfamily member 13
External IDsOMIM: 604472 MGI: 1916833 HomoloGene: 56971 GeneCards: TNFSF13
Orthologs
SpeciesHumanMouse
Entrez

8741

69583

Ensembl

ENSG00000161955

ENSMUSG00000089669

UniProt

O75888

Q9D777

RefSeq (mRNA)

NM_001159505
NM_023517

RefSeq (protein)

NP_001152977
NP_076006

Location (UCSC)Chr 17: 7.56 – 7.56 MbChr 11: 69.57 – 69.58 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[7] However, APRIL-deficient mice have also been reported to possess a reduced ability to support plasma cell survival.[8] 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.[9] Three alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported.

Interactions

TNFSF13 has been shown to interact with TNFRSF13B[10] and B-cell activating factor.[11]

Clinical significance

APRIL is being explored as a target for autoimmune diseases and B cell malignancies.[12] At least one anti-APRIL monoclonal antibody has been announced to enter phase I clinical trials for multiple myeloma.[13]

References
  1. GRCh38: Ensembl release 89: ENSG00000161955 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000089669 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 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 (September 1998). "APRIL, a new ligand of the tumor necrosis factor family, stimulates tumor cell growth". The Journal of Experimental Medicine. 188 (6): 1185–90. doi:10.1084/jem.188.6.1185. PMC 2212534. PMID 9743536.
  6. "Entrez Gene: TNFSF13 tumor necrosis factor (ligand) superfamily, member 13". National Library of Medicine. 10 October 2023. Retrieved 13 October 2023.
  7. 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 (February 2004). "APRIL-deficient mice have normal immune system development". Molecular and Cellular Biology. 24 (3): 997–1006. doi:10.1128/MCB.24.3.997-1006.2004. PMC 321448. PMID 14729948.
  8. Belnoue E, Pihlgren M, McGaha TL, Tougne C, Rochat AF, Bossen C, Schneider P, Huard B, Lambert PH, Siegrist CA (March 2008). "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. doi:10.1182/blood-2007-09-110858. PMID 18180376.
  9. Roth W, Wagenknecht B, Klumpp A, Naumann U, Hahne M, Tschopp J, Weller M (April 2001). "APRIL, a new member of the tumor necrosis factor family, modulates death ligand-induced apoptosis". Cell Death and Differentiation. 8 (4): 403–10. doi:10.1038/sj.cdd.4400827. PMID 11550092.
  10. 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 (November 2000). "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. doi:10.1074/jbc.M005224200. PMID 10956646.
  11. Roschke V, Sosnovtseva S, Ward CD, Hong JS, Smith R, Albert V, Stohl W, Baker KP, Ullrich S, Nardelli B, Hilbert DM, Migone TS (October 2002). "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. doi:10.4049/jimmunol.169.8.4314. PMID 12370363.
  12. Ryan MC, Grewal IS (2009-01-01). Grewal IS (ed.). Therapeutic Targets of the TNF Superfamily. Advances in Experimental Medicine and Biology. Vol. 647. New York: Springer. pp. 52–63. doi:10.1007/978-0-387-89520-8_4. ISBN 978-0-387-89519-2. PMID 19760066.
  13. "Development of a first in class APRIL fully blocking antibody BION-1301 for the treatment of multiple myeloma". AACR 2017 Proceedings. April 2017.

Further reading

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