Vitamin D induces SIRT1 activation through K610 deacetylation in colon cancer

Posttranslational modifications of epigenetic modifiers provide a flexible and timely mechanism for rapid adaptations to the dynamic environment of cancer cells. SIRT1 is an NAD+-dependent epigenetic modifier whose activity is classically associated with healthy aging and longevity, but its function...

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Autores: García-Martínez, José Manuel, Chocarro-Calvo, Ana, Martínez-Useros, Javier, Fernández-Aceñero, María Jesús, Fiuza, M Carmen, Cáceres-Rentero, José, De la Vieja, Antonio, Barbáchano, Antonio, Muñoz, Alberto, Larriba, María Jesús, García Jiménez, Custodia
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/16384
Acceso en línea:http://hdl.handle.net/20.500.12105/16384
Access Level:acceso abierto
Palabra clave:Receptors, Calcitriol
Colonic Neoplasms
Humans
Sirtuin 1
Calcitriol
Vitamins
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spelling Vitamin D induces SIRT1 activation through K610 deacetylation in colon cancerGarcía-Martínez, José ManuelChocarro-Calvo, AnaMartínez-Useros, JavierFernández-Aceñero, María JesúsFiuza, M CarmenCáceres-Rentero, JoséDe la Vieja, AntonioBarbáchano, AntonioMuñoz, AlbertoLarriba, María JesúsGarcía Jiménez, CustodiaReceptors, CalcitriolColonic NeoplasmsHumansSirtuin 1CalcitriolVitaminsPosttranslational modifications of epigenetic modifiers provide a flexible and timely mechanism for rapid adaptations to the dynamic environment of cancer cells. SIRT1 is an NAD+-dependent epigenetic modifier whose activity is classically associated with healthy aging and longevity, but its function in cancer is not well understood. Here, we reveal that 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3, calcitriol), the active metabolite of vitamin D (VD), promotes SIRT1 activation through auto-deacetylation in human colon carcinoma cells, and identify lysine 610 as an essential driver of SIRT1 activity. Remarkably, our data show that the post-translational control of SIRT1 activity mediates the antiproliferative action of 1,25(OH)2D3. This effect is reproduced by the SIRT1 activator SRT1720, suggesting that SIRT1 activators may offer new therapeutic possibilities for colon cancer patients who are VD deficient or unresponsive. Moreover, this might be extrapolated to inflammation and other VD deficiency-associated and highly prevalent diseases in which SIRT1 plays a prominent role.eLife Sciences PublicationsAgencia Estatal de Investigación (España)Instituto de Salud Carlos IIIComunidad de Madrid (España)King Juan Carlos University (España)Centro de Investigación Biomédica en Red - CIBERONC (Cáncer)20232023-08-3120232023-08-0220232023-08-02research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/16384reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/163842026-06-12T12:43:37Z
dc.title.none.fl_str_mv Vitamin D induces SIRT1 activation through K610 deacetylation in colon cancer
title Vitamin D induces SIRT1 activation through K610 deacetylation in colon cancer
spellingShingle Vitamin D induces SIRT1 activation through K610 deacetylation in colon cancer
García-Martínez, José Manuel
Receptors, Calcitriol
Colonic Neoplasms
Humans
Sirtuin 1
Calcitriol
Vitamins
title_short Vitamin D induces SIRT1 activation through K610 deacetylation in colon cancer
title_full Vitamin D induces SIRT1 activation through K610 deacetylation in colon cancer
title_fullStr Vitamin D induces SIRT1 activation through K610 deacetylation in colon cancer
title_full_unstemmed Vitamin D induces SIRT1 activation through K610 deacetylation in colon cancer
title_sort Vitamin D induces SIRT1 activation through K610 deacetylation in colon cancer
dc.creator.none.fl_str_mv García-Martínez, José Manuel
Chocarro-Calvo, Ana
Martínez-Useros, Javier
Fernández-Aceñero, María Jesús
Fiuza, M Carmen
Cáceres-Rentero, José
De la Vieja, Antonio
Barbáchano, Antonio
Muñoz, Alberto
Larriba, María Jesús
García Jiménez, Custodia
author García-Martínez, José Manuel
author_facet García-Martínez, José Manuel
Chocarro-Calvo, Ana
Martínez-Useros, Javier
Fernández-Aceñero, María Jesús
Fiuza, M Carmen
Cáceres-Rentero, José
De la Vieja, Antonio
Barbáchano, Antonio
Muñoz, Alberto
Larriba, María Jesús
García Jiménez, Custodia
author_role author
author2 Chocarro-Calvo, Ana
Martínez-Useros, Javier
Fernández-Aceñero, María Jesús
Fiuza, M Carmen
Cáceres-Rentero, José
De la Vieja, Antonio
Barbáchano, Antonio
Muñoz, Alberto
Larriba, María Jesús
García Jiménez, Custodia
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Agencia Estatal de Investigación (España)
Instituto de Salud Carlos III
Comunidad de Madrid (España)
King Juan Carlos University (España)
Centro de Investigación Biomédica en Red - CIBERONC (Cáncer)
dc.subject.none.fl_str_mv Receptors, Calcitriol
Colonic Neoplasms
Humans
Sirtuin 1
Calcitriol
Vitamins
topic Receptors, Calcitriol
Colonic Neoplasms
Humans
Sirtuin 1
Calcitriol
Vitamins
description Posttranslational modifications of epigenetic modifiers provide a flexible and timely mechanism for rapid adaptations to the dynamic environment of cancer cells. SIRT1 is an NAD+-dependent epigenetic modifier whose activity is classically associated with healthy aging and longevity, but its function in cancer is not well understood. Here, we reveal that 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3, calcitriol), the active metabolite of vitamin D (VD), promotes SIRT1 activation through auto-deacetylation in human colon carcinoma cells, and identify lysine 610 as an essential driver of SIRT1 activity. Remarkably, our data show that the post-translational control of SIRT1 activity mediates the antiproliferative action of 1,25(OH)2D3. This effect is reproduced by the SIRT1 activator SRT1720, suggesting that SIRT1 activators may offer new therapeutic possibilities for colon cancer patients who are VD deficient or unresponsive. Moreover, this might be extrapolated to inflammation and other VD deficiency-associated and highly prevalent diseases in which SIRT1 plays a prominent role.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-08-31
2023
2023-08-02
2023
2023-08-02
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/16384
url http://hdl.handle.net/20.500.12105/16384
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv eLife Sciences Publications
publisher.none.fl_str_mv eLife Sciences Publications
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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