Vitamin D induces SIRT1 activation through K610 deacetylation in colon cancer.

Autor: García-Martínez JM; Area of Physiology, Faculty Health Sciences, University Rey Juan Carlos, Alcorcón, Madrid, Spain., Chocarro-Calvo A; Area of Physiology, Faculty Health Sciences, University Rey Juan Carlos, Alcorcón, Madrid, Spain., Martínez-Useros J; Area of Physiology, Faculty Health Sciences, University Rey Juan Carlos, Alcorcón, Madrid, Spain.; Translational Oncology Division, OncoHealth Institute, Health Research Institute-University Hospital Fundación Jiménez Díaz-Universidad Autónoma de Madrid, Madrid, Spain., Fernández-Aceñero MJ; Department of Surgical Pathology, Hospital Clínico San Carlos, Madrid, Spain., Fiuza MC; Department of Surgery, University Hospital Fundación Alcorcón-Universidad Rey Juan Carlos, Alcorcón, Madrid, Spain., Cáceres-Rentero J; Area of Physiology, Faculty Health Sciences, University Rey Juan Carlos, Alcorcón, Madrid, Spain., De la Vieja A; Unidad de Tumores Endocrinos (UFIEC), Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.; CIBER de Cáncer, Instituto de Salud Carlos III, Madrid, Spain., Barbáchano A; CIBER de Cáncer, Instituto de Salud Carlos III, Madrid, Spain.; Instituto de Investigaciones Biomédicas 'Alberto Sols', Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid, Spain.; Instituto de Investigación Sanitaria del Hospital Universitario La Paz, Madrid, Spain., Muñoz A; CIBER de Cáncer, Instituto de Salud Carlos III, Madrid, Spain.; Instituto de Investigaciones Biomédicas 'Alberto Sols', Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid, Spain.; Instituto de Investigación Sanitaria del Hospital Universitario La Paz, Madrid, Spain., Larriba MJ; CIBER de Cáncer, Instituto de Salud Carlos III, Madrid, Spain.; Instituto de Investigaciones Biomédicas 'Alberto Sols', Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid, Spain.; Instituto de Investigación Sanitaria del Hospital Universitario La Paz, Madrid, Spain., García-Jiménez C; Area of Physiology, Faculty Health Sciences, University Rey Juan Carlos, Alcorcón, Madrid, Spain.
Jazyk: angličtina
Zdroj: ELife [Elife] 2023 Aug 02; Vol. 12. Date of Electronic Publication: 2023 Aug 02.
DOI: 10.7554/eLife.86913
Abstrakt: 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 D 3 (1,25(OH) 2 D 3, 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) 2 D 3 . 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.
Competing Interests: JG, AC, JM, MF, MF, JC, AD, AB, AM, ML, CG No competing interests declared
(© 2023, García-Martínez et al.)
Databáze: MEDLINE
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