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Rbx1,是VHL瘤抑制综合体和SCF泛基因酶的组成部分
T Kamura1, D M Koepp, M N Conrad
1Howard Hughes Medical Institute, Program in Molecular and Cell Biology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Science (New York, N.Y.)
|April 24, 1999
概括
·希佩尔-林道 (VHL) 瘤抑制蛋白质复合体包括Rbx1,将VHL与细胞无处不在联系起来. 这一发现增强了对VHL的理解.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 细胞生物学 细胞生物学
背景情况:
- 希佩尔-林道 (VHL) 瘤抑制基因在人类癌中经常发生突变.
- VHL蛋白在一个涉及转录延长和无处不在的复合体中起作用,包括Elongin B,Elongin C和Cullin-2.
- VHL复合体在癌症发病过程中的作用与其在蛋白质降解途径中的功能有关.
研究的目的:
- 为了研究内源性VHL复合物的完整组成.
- 为了确定VHL复合体内的新型蛋白相互作用.
- 阐明VHL复杂成分在细胞过程中的功能影响.
主要方法:
- 来自老鼠肝脏的VHL复合物的免疫沉.
- 质谱测量以确定相关的蛋白质.
- 与酵母基酸酶复合物的比较分析.
主要成果:
- 鼠肝中的内源VHL复合体含有Rbx1,这是一个具有RING-H2指纹样图案的保存蛋白质.
- Rbx1与卡林斯相互作用,这表明它在基质招募到无处不在的过程中发挥了作用.
- 酵母Rbx1的同类是SCF ((Cdc4) 基酶的关键组成部分,调节细胞循环的进展.
结论:
- VHL复合体的组成比以前知道的更广泛,包括Rbx1.
- 包括Rbx1建立了VHL瘤抑制器和核心无处不在机制之间的直接联系.
- 这些发现为在瘤抑制和细胞循环调节中的VHL功能背后的分子机制提供了新的见解.
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