维生素D通过K610脱乙酰化在结肠癌中诱导SIRT1激活。
Vitamin D induces SIRT1 activation through K610 deacetylation in colon cancer.
发表日期：2023 Aug 02
作者：
José Manuel García-Martínez, Ana Chocarro-Calvo, Javier Martínez-Useros, María Jesús Fernández-Aceñero, M Carmen Fiuza, José Cáceres-Rentero, Antonio De la Vieja, Antonio Barbáchano, Alberto Muñoz, María Jesús Larriba, Custodia García Jiménez
来源：
Epigenetics & Chromatin
摘要：
表观遗传修饰因子的翻译后修饰为癌细胞动态环境中的快速适应提供了一种灵活且及时的机制。SIRT1是一种依赖于NAD+的表观遗传修饰因子，其活性通常与健康老龄化和长寿相关，但它在癌症中的功能尚不明确。在这里，我们揭示了维生素D的活性代谢产物1α,25-二羟基维生素D3（1,25(OH)2D3，钙三醇）通过自身去乙酰化促进SIRT1在人类结肠癌细胞中的激活，并确定溶酶体蛋白610赖氨酸是SIRT1活性的关键驱动因子。值得注意的是，我们的数据显示SIRT1活性的翻译后控制介导了1,25(OH)2D3的抗增殖作用。这种效应可以通过SIRT1激活剂SRT1720复制，这表明SIRT1激活剂可能为VD缺乏或无反应的结肠癌患者提供新的治疗可能性。此外，这可能可以推广到炎症以及其他与VD缺乏相关且高发病率的疾病，其中SIRT1起着重要作用。© 2023, García-Martínez等人。
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.© 2023, García-Martínez et al.