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AIDing cancer treatment: Reducing AID activity via HSP90 inhibition

The activation induced deaminase (AID) catalyses the two key events underlying humoral adaptive immunity: class switch recombination and somatic hypermutation of antibody genes in B lymphocytes. AID accomplishes this task by directly deaminating cytosines within the genomic immunoglobulin locus, the...

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Detalles Bibliográficos
Autores principales: Rebhandl, Stefan, Geisberger, Roland
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4677455/
https://www.ncbi.nlm.nih.gov/pubmed/26151367
http://dx.doi.org/10.1002/eji.201545832
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author Rebhandl, Stefan
Geisberger, Roland
author_facet Rebhandl, Stefan
Geisberger, Roland
author_sort Rebhandl, Stefan
collection PubMed
description The activation induced deaminase (AID) catalyses the two key events underlying humoral adaptive immunity: class switch recombination and somatic hypermutation of antibody genes in B lymphocytes. AID accomplishes this task by directly deaminating cytosines within the genomic immunoglobulin locus, thereby triggering a complex mutagenic process eventually leading to improved effector function of antibodies. However, it has long been noticed that AID can be aberrantly expressed in cancer and that its activity is not absolutely restricted to antibody genes, as substantial genome‐wide off‐target mutations have been observed, which contribute to tumorigenesis and clonal evolution of AID‐expressing malignancies. In this issue of the European Journal of Immunology, Montamat‐Sicotte et al. [Eur. J. Immunol. 2015. 45: 2365–2376] investigate the feasibility and efficacy of in vivo inhibition of AID with HSP90 inhibitors in a mouse model of B‐cell leukemia and in vitro with a human breast cancer cell line, thereby demonstrating that cancer patients may benefit from preventing noncanonical AID functions.
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spelling pubmed-46774552015-12-14 AIDing cancer treatment: Reducing AID activity via HSP90 inhibition Rebhandl, Stefan Geisberger, Roland Eur J Immunol Highlights The activation induced deaminase (AID) catalyses the two key events underlying humoral adaptive immunity: class switch recombination and somatic hypermutation of antibody genes in B lymphocytes. AID accomplishes this task by directly deaminating cytosines within the genomic immunoglobulin locus, thereby triggering a complex mutagenic process eventually leading to improved effector function of antibodies. However, it has long been noticed that AID can be aberrantly expressed in cancer and that its activity is not absolutely restricted to antibody genes, as substantial genome‐wide off‐target mutations have been observed, which contribute to tumorigenesis and clonal evolution of AID‐expressing malignancies. In this issue of the European Journal of Immunology, Montamat‐Sicotte et al. [Eur. J. Immunol. 2015. 45: 2365–2376] investigate the feasibility and efficacy of in vivo inhibition of AID with HSP90 inhibitors in a mouse model of B‐cell leukemia and in vitro with a human breast cancer cell line, thereby demonstrating that cancer patients may benefit from preventing noncanonical AID functions. John Wiley and Sons Inc. 2015-07-07 2015-08 /pmc/articles/PMC4677455/ /pubmed/26151367 http://dx.doi.org/10.1002/eji.201545832 Text en © 2015 The Authors. European Journal of Immunology published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Highlights
Rebhandl, Stefan
Geisberger, Roland
AIDing cancer treatment: Reducing AID activity via HSP90 inhibition
title AIDing cancer treatment: Reducing AID activity via HSP90 inhibition
title_full AIDing cancer treatment: Reducing AID activity via HSP90 inhibition
title_fullStr AIDing cancer treatment: Reducing AID activity via HSP90 inhibition
title_full_unstemmed AIDing cancer treatment: Reducing AID activity via HSP90 inhibition
title_short AIDing cancer treatment: Reducing AID activity via HSP90 inhibition
title_sort aiding cancer treatment: reducing aid activity via hsp90 inhibition
topic Highlights
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4677455/
https://www.ncbi.nlm.nih.gov/pubmed/26151367
http://dx.doi.org/10.1002/eji.201545832
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