Department of Biomedical Sciences, University of Padova, Padova 35122, Italy.
Institute of Transformative Bio-Molecules, Nagoya University, Nagoya 464-8601, Japan.
Open Biol. 2023 Feb;13(2):220220. doi: 10.1098/rsob.220220. Epub 2023 Feb 22.
CK2 is a Ser/Thr protein kinase composed of two catalytic (/') subunits and a non-catalytic β-subunit dimer, whose activity is often abnormally high in cancer cells. The concept that CK2 may be dispensable for cell survival has been challenged by the finding that viable CK2/' knock-out myoblast clones still express small amounts of an N-terminally deleted ' subunit generated during the CRISPR/Cas9 procedure. Here we show that, although the overall CK2 activity of these CK2/Δ' (KO) cells is less than 10% compared to wild-type (WT) cells, the number of phosphosites with the CK2 consensus is comparable to that of WT cells. A more in-depth analysis, however, reveals that the two phosphoproteomes are not superimposable according to a number of criteria, notably a functional analysis of the phosphoproteome found in the two types of cells, and variable sensitivity of the phosphosites to two structurally unrelated CK2 inhibitors. These data support the idea that a minimal CK2 activity, as in KO cells, is sufficient to perform basic housekeeping functions essential for cell survival, but not to accomplish several specialized tasks required upon cell differentiation and transformation. From this standpoint, a controlled downregulation of CK2 would represent a safe and valuable anti-cancer strategy.
CK2 是一种丝氨酸/苏氨酸蛋白激酶，由两个催化 (/') 亚基和一个非催化的β-亚基二聚体组成，其活性在癌细胞中通常异常升高。CK2 可能对细胞存活不是必需的这一概念受到了挑战，因为发现在 CRISPR/Cas9 过程中产生的 N 端缺失 '亚基的存活 CK2/'敲除成肌细胞克隆仍然表达少量的 '亚基。在这里，我们表明，尽管这些 CK2/Δ'（KO）细胞的总 CK2 活性与野生型（WT）细胞相比小于 10%，但具有 CK2 共有序列的磷酸化位点数量与 WT 细胞相当。然而，更深入的分析表明，根据多个标准，这两个磷酸蛋白质组不能叠加，特别是对两种细胞中磷酸蛋白质组的功能分析，以及磷酸位点对两种结构上不相关的 CK2 抑制剂的可变敏感性。这些数据支持这样一种观点，即像 KO 细胞中的最小 CK2 活性足以执行基本的维持细胞存活所必需的管家功能，但不足以完成细胞分化和转化所需的几个专门任务。从这个角度来看，CK2 的受控下调将代表一种安全且有价值的抗癌策略。
