Targeting of NEDD8 and its conjugates for proteasomal degradation by NUB1.
Targeting of NEDD8 and its conjugates for proteasomal degradation by NUB1.
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DOI：
10.1074/jbc.m108636200
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发表时间：
2001-12-07
影响因子：
4.8
通讯作者：
Yeh, ETH
中科院分区：
文献类型：
--
作者：
Kamitani, T;Kito, K;Yeh, ETH
NEDD 8是一种泛素样蛋白，通过与cullin家族成员结合来控制重要的生物事件。最近，我们鉴定了NEDD 8缀合系统的负调节因子NUB 1，其与NEDD 8相互作用并在转录后下调NEDD 8表达（Kito，K.，叶，E. T. H.，和Kamitani，T.（2001）J.Biol.Chem.276，20603-20609）。在这里，我们表明，NUB 1具有一个泛素样结构域的N-末端区域，并结合到S5 a的19 S蛋白酶体激活剂（PA 700）。GST pull-down分析显示，NUB 1的过表达导致NEDD 8与GST-S5 a结合物的更大沉淀，表明NUB 1可能在S5 a和NEDD 8之间具有衔接子功能。此外，蛋白酶体抑制剂完全阻断NUB 1介导的NEDD 8表达下调。这些结果表明，NUB 1招募NEDD 8及其缀合物到蛋白酶体进行降解，提供了NEDD 8缀合系统和蛋白酶体降解途径之间的直接功能联系。
NEDD8 is a ubiquitin-like protein that controls vital biological events through its conjugation to cullin family members. Recently, we identified a negative regulator of the NEDD8 conjugation system, NUB1, which interacts with NEDD8 and down-regulates NEDD8 expression post-transcriptionally (Kito, K., Yeh, E. T. H., and Kamitani, T. (2001) J. Biol. Chem. 276, 20603-20609). Here, we show that NUB1 possesses a ubiquitin-like domain at the N-terminal region and binds to S5a of the 19 S proteasome activator (PA700). A GST pull-down assay revealed that the overexpression of NUB1 leads to a greater precipitation of NEDD8 conjugates with GST-S5a, suggesting that NUB1 might have an adaptor function between S5a and NEDD8. Furthermore, proteasome inhibitors completely block NUB1-mediated down-regulation of NEDD8 expression. These results suggest that NUB1 recruits NEDD8 and its conjugates to the proteasome for degradation, providing a direct functional link between the NEDD8 conjugation system and the proteasomal degradation pathway.