在DNA修复酶ATM调节CD13表达和细胞迁移
Louise K Stevenson1,2, Amy J Page1, Matthew Dowson1
1School of Biosciences, Healthy Lifespan and Neuroscience Institutes, University of Sheffield, Sheffield, United Kingdom.
Frontiers in cell and developmental biology
|June 27, 2024
概括
该ATM激酶通过抑制其降解来调节氨基酶-N (CD13) 蛋白质水平,而不是mRNA. 这种ATM-CD13通路对于细胞迁移至关重要.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
背景情况:
- 传统上,ATM 激酶是用于修复DNA损伤的.
- ATM具有非正规的作用,包括血管生成,可能通过p38信号传递.
- ATM,p38信号传递和金属蛋白酶之间的联系尚未完全理解.
研究的目的:
- 研究ATM对氨基酶-N (CD13) 表达的调节作用.
- 阐明ATM影响CD13蛋白水平的机制.
- 为了确定ATM-CD13相互作用在细胞迁移中的功能意义.
主要方法:
- 西方涂抹用于评估野生类型和ATM淘汰细胞中的蛋白质水平.
- 定量PCR (qPCR) 和对公共RNAseq数据的分析,以评估mRNA水平.
- 用ATM抑制剂 (ATMi) 和蛋白质酶抑制剂进行治疗.
- 细胞迁移测定. 细胞迁移测定.
主要成果:
- ATM活动与CD13蛋白表达具有正相关性.
- ATM 调节 CD13 在蛋白质水平,而不是mRNA,表明控制蛋白质降解.
- 蛋白质酶抑制可以恢复ATMi治疗细胞中的CD13水平.
- 抑制ATM或CD13会影响细胞迁移,没有附加效应.
结论:
- 而ATM则对CD13蛋白的降解产生负面调节.
- 在相同的途径内,ATM和CD13的功能会影响细胞迁移.
- 这项研究揭示了ATM和CD13之间的新功能相互作用.
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