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核PTEN调节了人类前列腺癌细胞系中的甲基酸盐生物合成

Zoe N Loh^1,2, Mu-En Wang^1,2, Changxin Wan³

¹Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA.

|August 25, 2023

概括

核PTEN通过与MTHFD1.1相互作用来调节胺代谢,特别是胺基酸盐 (dTMP) 生物合成. 这一发现揭示了PTEN在代谢控制中的新型核作用.

科学领域:

分子生物学分子生物学
癌症生物学癌症生物学
代谢调节代谢调节代谢调节

背景情况:

瘤抑制剂PTEN (在染色体10上删除的酸酶和张素同类物) 对细胞过程至关重要,包括新陈代谢.
在细胞质中PTEN的作用涉及调节PI3K/AKT/mTORC1通路的脂质酸酶活性.
在细胞核内,PTEN的代谢功能尚不清楚.

研究的目的:

研究PTEN在代谢调节中的核功能.
确定PTEN在pyrimidine新陈代谢中的作用,特别是 de novo thymidylate (dTMP) 生物合成.

主要方法:

使用一种功能获取策略,专门针对PTEN到血和细胞核.
研究了PTEN与参与核酸生物合成的关键酶的相互作用.

主要成果:

证明核PTEN显著促进了de novo基酸盐 (dTMP) 生物合成.
鉴定了PTEN和甲基基酸脱酶1 (MTHFD1),这是叶酸代谢中的关键酶之间的相互作用.
表明PTEN会影响5,10-甲基四叶酸的产生,这是一种对thymidylate synthase (TYMS) 必不可少的辅因子.

结论:

在调节dTMP生物合成方面,PTEN具有以前未知的核功能.
这种PTEN在pyrimidine代谢中的核作用对癌症治疗有潜在的影响,特别是对于具有核排除PTEN的前列腺癌细胞.

关键词:

癌症癌症癌症癌症癌症代谢细分化的代谢细分.核电 PTEN 核电 PTEN 核电 PTEN 提米基酸盐生物合成

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