一个细胞表面受体的利波卡林24p3选择性介导细胞亡和铁的吸收
Laxminarayana R Devireddy1, Claude Gazin, Xiaochun Zhu
1Howard Hughes Medical Institute, Programs in Gene Function and Expression and Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Cell
|December 27, 2005
概括
24p3受体 (24p3R) 调节细胞亡和铁水平. BCR-ABL coprotein 阻断了 24p3R,但是 imatinib 恢复了它,从而诱导了癌细胞的亡.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 鼠标的卡林24p3蛋白质参与了亡和铁运输.
- 24p3 (24p3R) 的细胞表面受体以前没有表征.
研究的目的:
- 克隆和表征24p3细胞表面受体 (24p3R).
- 研究24p3R在铁运输和亡中的作用.
- 探索24p3R,BCR-ABL蛋白和伊马替尼治疗之间的关系.
主要方法:
- 对24p3R基因进行克隆.
- 基于细胞的测试来评估铁的吸收和亡.
- 对24p3,铁和BCR-ABL.反应中的基因表达的分析.
- 用伊马替尼治疗BCR-ABL表达细胞.
主要成果:
- 异位24p3R表达使细胞能够根据结合体铁含量控制铁含量和亡.
- 含铁的24p3会增加细胞内铁;缺乏铁的24p3会诱导Bim和亡.
- BCR-ABL激活24p3并抑制24p3R,导致对24p3.3的抵抗.
- 伊马替尼抑制BCR-ABL,诱导BCR-ABL(+) 细胞中的24p3R表达和亡.
结论:
- 细胞内铁调节是新型亡途径的关键组成部分.
- 这一途径与BCR-ABL诱导的骨髓增殖性疾病有关.
- 准24p3R为BCR-ABL相关癌症提供了一个潜在的治疗策略.
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