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SIRT3:癌症中的癌基因与肿瘤抑制因子

SIRT3: Oncogene and Tumor Suppressor in Cancer.

作者信息

Torrens-Mas Margalida, Oliver Jordi, Roca Pilar, Sastre-Serra Jorge

机构信息

Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d´Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears. Cra de Valldemossa, km 7.5, 07122 Palma, Illes Balears 07122, Spain.

Ciber Fisiopatología Obesidad y Nutrición (CB06/03) Instituto Salud Carlos III, Madrid 28029, Spain.

出版信息

Cancers (Basel). 2017 Jul 12;9(7):90. doi: 10.3390/cancers9070090.

Abstract

Sirtuin 3 (SIRT3), the major deacetylase in mitochondria, plays a crucial role in modulating oxygen reactive species (ROS) and limiting the oxidative damage in cellular components. SIRT3 targets different enzymes which regulate mitochondrial metabolism and participate in ROS detoxification, such as the complexes of the respiratory chain, the isocitrate dehydrogenase, or the manganese superoxide dismutase. Thus, SIRT3 activity is essential in maintaining mitochondria homeostasis and has recently received great attention, as it is considered a fidelity protein for mitochondrial function. In some types of cancer, SIRT3 functions as a tumoral promoter, since it keeps ROS levels under a certain threshold compatible with cell viability and proliferation. On the contrary, other studies describe SIRT3 as a tumoral suppressor, as SIRT3 could trigger cell death under stress conditions. Thus, SIRT3 could have a dual role in cancer. In this regard, modulation of SIRT3 activity could be a new target to develop more personalized therapies against cancer.

摘要

沉默调节蛋白3(SIRT3)是线粒体中的主要去乙酰化酶,在调节氧活性物质(ROS)和限制细胞成分的氧化损伤方面发挥着关键作用。SIRT3作用于不同的酶,这些酶调节线粒体代谢并参与ROS解毒,如呼吸链复合物、异柠檬酸脱氢酶或锰超氧化物歧化酶。因此,SIRT3活性对于维持线粒体稳态至关重要,并且最近受到了极大关注,因为它被认为是线粒体功能的保真蛋白。在某些类型的癌症中,SIRT3作为肿瘤促进因子发挥作用,因为它将ROS水平维持在与细胞活力和增殖相容的特定阈值以下。相反,其他研究将SIRT3描述为肿瘤抑制因子,因为SIRT3在应激条件下可触发细胞死亡。因此,SIRT3在癌症中可能具有双重作用。在这方面,调节SIRT3活性可能成为开发更具个性化癌症治疗方法的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10e2/5532626/5078c8a4ecd5/cancers-09-00090-g001.jpg

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