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蛋白激酶 CK2-在癌细胞生物学中的多种作用和治疗潜力。

Protein kinase CK2 - diverse roles in cancer cell biology and therapeutic promise.

机构信息

Research Service, Minneapolis VA Health Care System, Minneapolis, MN, 55417, USA.

Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, 55455, USA.

出版信息

Mol Cell Biochem. 2023 Apr;478(4):899-926. doi: 10.1007/s11010-022-04558-2. Epub 2022 Sep 17.

Abstract

The association of protein kinase CK2 (formerly casein kinase II or 2) with cell growth and proliferation in cells was apparent at early stages of its investigation. A cancer-specific role for CK2 remained unclear until it was determined that CK2 was also a potent suppressor of cell death (apoptosis); the latter characteristic differentiated its function in normal versus malignant cells because dysregulation of both cell growth and cell death is a universal feature of cancer cells. Over time, it became evident that CK2 exerts its influence on a diverse range of cell functions in normal as well as in transformed cells. As such, CK2 and its substrates are localized in various compartments of the cell. The dysregulation of CK2 is documented in a wide range of malignancies; notably, by increased CK2 protein and activity levels with relatively moderate change in its RNA abundance. High levels of CK2 are associated with poor prognosis in multiple cancer types, and CK2 is a target for active research and testing for cancer therapy. Aspects of CK2 cellular roles and targeting in cancer are discussed in the present review, with focus on nuclear and mitochondrial functions and prostate, breast and head and neck malignancies.

摘要

蛋白激酶 CK2(原称酪蛋白激酶 II 或 2)与细胞生长和增殖的关联在其研究的早期阶段就已经很明显。直到确定 CK2 也是细胞死亡(凋亡)的有效抑制剂,CK2 在癌症中的特定作用仍不清楚;后一特征将其在正常细胞与恶性细胞中的功能区分开来,因为细胞生长和细胞死亡的失调是癌细胞的普遍特征。随着时间的推移,越来越明显的是,CK2 对正常细胞和转化细胞中的多种细胞功能都有影响。因此,CK2 及其底物在细胞的各个区域都有定位。CK2 的失调在多种恶性肿瘤中都有记录;特别是 CK2 的蛋白和活性水平增加,而其 RNA 丰度相对适中。在多种癌症类型中,高水平的 CK2 与预后不良相关,CK2 是癌症治疗的积极研究和测试的靶点。本综述讨论了 CK2 在癌症中的细胞作用和靶向作用,重点关注核和线粒体功能以及前列腺癌、乳腺癌和头颈部恶性肿瘤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e044/9483426/78f818b24e08/11010_2022_4558_Fig1_HTML.jpg

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