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ING3 蛋白在正常人体组织中的表达谱提示其在细胞生长和自我更新中的作用。

ING3 protein expression profiling in normal human tissues suggest its role in cellular growth and self-renewal.

机构信息

Department of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Oncology, Southern Alberta Cancer Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

Department of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Oncology, Southern Alberta Cancer Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Pathology & Laboratory Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

出版信息

Eur J Cell Biol. 2015 May;94(5):214-22. doi: 10.1016/j.ejcb.2015.03.002. Epub 2015 Mar 14.

Abstract

Members of the INhibitor of Growth (ING) family of proteins act as readers of the epigenetic code through specific recognition of the trimethylated form of lysine 4 of histone H3 (H3K4Me3) by their plant homeodomains. The founding member of the family, ING1, was initially identified as a tumor suppressor with altered regulation in a variety of cancer types. While alterations in ING1 and ING4 levels have been reported in a variety of cancer types, little is known regarding ING3 protein levels in normal or transformed cells due to a lack of reliable immunological tools. In this study we present the characterization of a new monoclonal antibody we have developed against ING3 that specifically recognizes human and mouse ING3. The antibody works in western blots, immunofluorescence, immunoprecipitation and immunohistochemistry. Using this antibody we show that ING3 is most highly expressed in small intestine, bone marrow and epidermis, tissues in which cells undergo rapid proliferation and renewal. Consistent with this observation, we show that ING3 is expressed at significantly higher levels in proliferating versus quiescent epithelial cells. These data suggest that ING3 levels may serve as a surrogate for growth rate, and suggest possible roles for ING3 in growth and self renewal and related diseases such as cancer.

摘要

ING 家族蛋白成员通过其植物同源结构域特异性识别组蛋白 H3 赖氨酸 4 的三甲基化形式(H3K4Me3),充当表观遗传密码的读取器。ING1 作为该家族的创始成员,最初被鉴定为一种肿瘤抑制因子,在多种癌症类型中存在调节异常。尽管在多种癌症类型中已经报道了 ING1 和 ING4 水平的改变,但由于缺乏可靠的免疫工具,对于正常或转化细胞中 ING3 蛋白水平知之甚少。在这项研究中,我们介绍了一种针对 ING3 开发的新单克隆抗体的特性,该抗体特异性识别人源和鼠源 ING3。该抗体可用于 Western blot、免疫荧光、免疫沉淀和免疫组织化学。使用该抗体,我们表明 ING3 在小肠、骨髓和表皮中表达水平最高,这些组织中的细胞经历快速增殖和更新。与这一观察结果一致的是,我们表明 ING3 在增殖的上皮细胞中表达水平显著高于静止的上皮细胞。这些数据表明,ING3 水平可能作为生长速度的替代指标,并提示 ING3 在生长和自我更新以及相关疾病(如癌症)中的可能作用。

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