定量蛋白质组学揭示了 ALKBH4 的新功能。
Quantitative proteomics revealed new functions of ALKBH4.
机构信息
Department of Chemistry, University of California, Riverside, California, USA.
Environmental Toxicology Graduate Program, University of California, Riverside, California, USA.
出版信息
Proteomics. 2022 Apr;22(7):e2100231. doi: 10.1002/pmic.202100231. Epub 2022 Jan 5.
ALKBH4 is a versatile demethylase capable of catalyzing the demethylation of monomethylated lysine-84 on actin and N -methyladenine in DNA. In this study, we conducted a quantitative proteomic experiment to reveal the altered expression of proteins in HEK293T cells upon genetic ablation of ALKBH4. Our results showed markedly diminished levels of GSTP1 and HSPB1 proteins in ALKBH4-depleted cells, which emanate from an augmented expression level of DNA (cytosine-5)-methyltransferase 1 (DNMT1) and the ensuing elevated cytosine methylation in the promoter regions of GSTP1 and HSPB1 genes. Together, our results revealed a role of ALKBH4 in modulating DNA cytosine methylation through regulating the expression level of DNMT1 protein.
ALKBH4 是一种多功能的去甲基酶，能够催化肌动蛋白上赖氨酸-84 的单甲基化和 DNA 中的 N -甲基腺嘌呤的去甲基化。在这项研究中，我们进行了定量蛋白质组学实验，以揭示在 HEK293T 细胞中 ALKBH4 基因缺失后蛋白质表达的变化。我们的结果表明，ALKBH4 缺失细胞中的 GSTP1 和 HSPB1 蛋白水平明显降低，这源于 DNA（胞嘧啶-5）-甲基转移酶 1（DNMT1）表达水平的增加，以及 GSTP1 和 HSPB1 基因启动子区域中胞嘧啶甲基化水平的升高。总之，我们的结果揭示了 ALKBH4 通过调节 DNMT1 蛋白的表达水平来调节 DNA 胞嘧啶甲基化的作用。
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