DCC基因产物通过一种需要受体蛋白解的机制诱导亡
P Mehlen1, S Rabizadeh, S J Snipas
1Program on Aging, The Burnham Institute, La Jolla, California 92037, USA.
Nature
|October 31, 1998
概括
在结肠直肠癌 (DCC) 中被删除的基因通过诱导其连接体,网林-1 缺席时诱导亡来抑制瘤. 通过caspase-3进行DCC裂变对于这种瘤抑制功能至关重要.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 细胞信号传递 细胞信号传递
背景情况:
- 大肠直肠癌的发展涉及基因突变,包括候选瘤抑制剂DCC.
- DCC编码了网-1受体,对于轴突引导至关重要.
- DCC表达的丧失与瘤性相关,但其机制尚不清楚.
研究的目的:
- 阐明DCC抑制瘤形成的机制.
- 调查网林-1结合和酶裂解在DCC功能中的作用.
主要方法:
- 研究了DCC在带有和没有netrin-1的细胞亡上的作用.
- 识别了DCC作为一个caspase基质.
- 突变了DCC上的caspase-3分裂部位,以评估其对亡的影响.
主要成果:
- DCC 诱导了独立于网林-1 结合的亡.
- 结合DCC的Netrin-1可以抑制细胞灭亡.
- 卡斯巴酶-3对DCC的裂变是其亲细胞灭绝活性所必需的,特别是在Asp 1,290.0时.
结论:
- 当网林-1无法使用时,DCC通过促进亡来作为瘤抑制剂发挥作用.
- 这种亲细胞灭绝的功能是由酶级联介导的,需要在Asp 1,290.0时进行DCC裂变.
- DCC的机制涉及通过酶介导的裂变诱导结合体独立的亡,这对于瘤抑制至关重要.
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