NUP98-BPTF通过PIM1上调促进瘤转化
Mina Noura1, Sakura Tomita1, Takahiko Yasuda2
1Division of Cellular and Genetic Sciences, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Cancer medicine
|June 28, 2024
概括
NUP98-BPTF (NB) 融合蛋白通过上调PIM1原瘤基因来驱动白血病,促进细胞转化和生存. 向PIM1或mTORC1为NB融合阳性白血病提供了潜在的治疗策略.
科学领域:
- 血液学 血液学 血液学
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- 核蛋白98 (NUP98) 融合蛋白与白血病的发病有关.
- 在T细胞急性淋巴细胞白血病 (T-ALL) 中发现的NUP98-BPTF (NB) 融合被怀疑通过异常基因调节驱动白血病发生.
- 通过NB融合调节的特定目标基因和途径在很大程度上仍未知.
研究的目的:
- 调查NB融合蛋白的致癌性质和下游目标.
- 阐明NB有助于白血病细胞转化和生存的机制.
主要方法:
- 对可诱导多克西环素的NB表达载体在小鼠NIH3T3纤维细胞和人类Jurkat T-ALL细胞中的lentiviral转导.
- 对基因表达,蛋白质信号通路 (MYC,mTORC1) 和细胞活性的分析.
- 研究了PIM1和mTORC1在NB介导细胞转化中的作用.
主要成果:
- NB融合蛋白促进NIH3T3细胞转化,通过上调原瘤基因PIM1.1.
- 通过促进体结合,NB通过转录调节PIM1,激活MYC和mTORC1信号通路.
- NB增强了Jurkat T-ALL细胞的存活率,因为它通过非活性化BAD的亲细胞亡蛋白.
结论:
- NB融合蛋白在细胞转化和生存中起着至关重要的作用.
- 确定PIM1是NB融合的一个关键下游目标.
- 针对NB融合,PIM1或mTORC1信号提供了NB融合阳性白血病的潜在治疗途径.
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