Vitamin D induces SIRT1 activation through K610 deacetylation in colon cancer
Vitamin D induces SIRT1 activation through K610 deacetylation in colon cancer
ABSTRACT 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.
Fern¨￠ndez-Ace?ero Mar¨aa Jes¨2s、C¨￠ceres-Rentero Jose、Barb¨￠chano Antonio、Mu?oz Alberto、De la Vieja Antonio、Fiuza M. Carmen、Garc¨aa-Mart¨anez Jos¨| Manuel、Larriba Mar¨aa Jes¨2s、Garc¨aa-Jim¨|nez Custodia、Mart¨anez-Useros Javier、Chocarro-Calvo Ana
Department of Surgical Pathology, Hospital Cl¨anico San CarlosFaculty Health Sciences, University Rey Juan CarlosInstituto de Salud Carlos III||Instituto de Investigaciones Biom¨|dicas ?°Alberto Sols?± Universidad Aut¨?noma de Madrid||Instituto de Investigaci¨?n Sanitaria del Hospital Universitario La PazInstituto de Salud Carlos III||Instituto de Investigaciones Biom¨|dicas ?°Alberto Sols?± Universidad Aut¨?noma de Madrid||Instituto de Investigaci¨?n Sanitaria del Hospital Universitario La PazInstituto de Salud Carlos III||Instituto de Salud Carlos IIIDepartment of Surgery, University Hospital Fundaci¨?n Alcorc¨?n-Universidad Rey Juan CarlosFaculty Health Sciences, University Rey Juan CarlosInstituto de Salud Carlos III||Instituto de Investigaciones Biom¨|dicas ?°Alberto Sols?± Universidad Aut¨?noma de Madrid||Instituto de Investigaci¨?n Sanitaria del Hospital Universitario La PazFaculty Health Sciences, University Rey Juan CarlosFaculty Health Sciences, University Rey Juan Carlos||Translational Oncology Division, OncoHealth Institute, Health Research Institute-University Hospital Fundaci¨?n Jim¨|nez D¨aaz-Universidad Aut¨?noma de MadridFaculty Health Sciences, University Rey Juan Carlos
肿瘤学基础医学生物化学
colorectal cancervitamin DVDRSIRT1acetylation
Fern¨￠ndez-Ace?ero Mar¨aa Jes¨2s,C¨￠ceres-Rentero Jose,Barb¨￠chano Antonio,Mu?oz Alberto,De la Vieja Antonio,Fiuza M. Carmen,Garc¨aa-Mart¨anez Jos¨| Manuel,Larriba Mar¨aa Jes¨2s,Garc¨aa-Jim¨|nez Custodia,Mart¨anez-Useros Javier,Chocarro-Calvo Ana.Vitamin D induces SIRT1 activation through K610 deacetylation in colon cancer[EB/OL].(2025-03-28)[2025-05-28].https://www.biorxiv.org/content/10.1101/2023.02.22.529558.点此复制
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