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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Conjugation of the ubiquitin-like protein NEDD8 to cullin-2 is linked to von Hippel-Lindau tumor suppressor function
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Conjugation of the ubiquitin-like protein NEDD8 to cullin-2 is linked to von Hippel-Lindau tumor suppressor function

机译:泛素样蛋白NEDD8与cullin-2的结合与von Hippel-Lindau抑癌功能有关

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摘要

The von Hippel-Lindau tumor suppressor protein PVHL assembles with cullin-2 (hCUL-2) and elongin B/C forming a protein complex, CBC(vhl), that resembles SKPI-CDC53-F-box protein ubiquitin ligases. Here, we show that hCUL-2 is modified by the conserved ubiquitin-like protein NEDDS and that NEDDS-hCUL-2 conjugates are part of CBC(vhl) complexes in vivo. Remarkably, the formation of these conjugates is stimulated by the P(vhl) tumor suppressor. A tumorigenic P(VHL) variant, however, is essentially deficient in this activity. Thus, ligation of NEDDS to hCUL.2 is linked to PVHL activity and may be important for PVHL tumor suppressor function.
机译:von Hippel-Lindau肿瘤抑制蛋白PVHL与cullin-2(hCUL-2)和Elongin B / C组装,形成类似于SKPI-CDC53-F-box蛋白泛素连接酶的蛋白复合物CBC(vhl)。在这里,我们显示hCUL-2被保守的泛素样蛋白NEDDS修饰,并且NEDDS-hCUL-2缀合物是体内CBC(vhl)复合物的一部分。显着地,这些缀合物的形成被P(vhl)肿瘤抑制剂刺激。然而,致瘤的P(VHL)变体在该活性上基本上是不足的。因此,NEDDS与hCUL.2的连接与PVHL活性相关,可能对PVHL肿瘤抑制功能很重要。

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