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Grant support

This work was supported by Dutch Cancer Society Grant UvA 2007-3750, the Swiss National Science Foundation (to P. S.), and the European Union (PROSPECTS (Grant Agreement HEALTH-F4-2008-201648) and TRIDENT (Grant Agreement FP6-LIFESCIHEALTH-37686); both to L. S.).

Analysis of institutional authors

Van Der Sloot AmAuthorSerrano LCorresponding Author

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March 25, 2020
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The design and characterization of receptor-selective APRIL variants

Publicated to:Journal Of Biological Chemistry. 287 (44): 37434-37446 - 2012-10-26 287(44), DOI: 10.1074/jbc.M112.406090

Authors: Kimberley, FC; van der Sloot, AM; Guadagnoli, M; Cameron, K; Schneider, P; Marquart, JA; Versloot, M; Serrano, L; Medema, JP

Affiliations

Inst Catalana Rec & Estudis Avancats, Barcelona 08010, Spain - Author
Laboratory of Experimental Oncology and Radiobiology, Center for Experimental Molecular Medicine, University of Amsterdam, Amsterdam 1105 A2, The Netherlands. - Author
Univ Amsterdam, Acad Med Ctr, Ctr Expt Mol Med, Lab Expt Oncol & Radiobiol, NL-1105 Amsterdam, Netherlands - Author
Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland - Author
Univ Pompeu Fabra, Ctr Genom Regulat, EMBL CRG Syst Biol Res Unit, Barcelona 08003, Spain - Author
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Abstract

A proliferation-inducing ligand (APRIL), a member of the TNF ligand superfamily with an important role in humoral immunity, is also implicated in several cancers as a prosurvival factor. APRIL binds two different TNF receptors, B cell maturation antigen (BCMA) and transmembrane activator and cylclophilin ligand interactor (TACI), and also interacts independently with heparan sulfate proteoglycans. Because APRIL shares binding of the TNF receptors with B cell activation factor, separating the precise signaling pathways activated by either ligand in a given context has proven quite difficult. In this study, we have used the protein design algorithm FoldX to successfully generate a BCMA-specific variant of APRIL, APRIL-R206E, and two TACI-selective variants, D132F and D132Y. These APRIL variants show selective activity toward their receptors in several in vitro assays. Moreover, we have used these ligands to show that BCMA and TACI have a distinct role in APRIL-induced B cell stimulation. We conclude that these ligands are useful tools for studying APRIL biology in the context of individual receptor activation.

Keywords

Agonist antibodyApoptosisBaff-rBcmaBindingLigandNecrosis-factor familyNf-kappa-bTaciTnf receptor

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Journal Of Biological Chemistry due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2012, it was in position 62/290, thus managing to position itself as a Q1 (Primer Cuartil), in the category Biochemistry & Molecular Biology.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2025-08-02:

  • WoS: 8
  • Scopus: 9
  • Europe PMC: 7

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-08-02:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 40.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 47 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 15.25.
  • The number of mentions on the social network Facebook: 1 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Netherlands; Switzerland.

the author responsible for correspondence tasks has been SERRANO PUBUL, LUIS.