Inhibition of NEDD8-conjugation pathway by novel molecules: potential approaches to anticancer therapy.
Inhibition of NEDD8-conjugation pathway by novel molecules: potential approaches to anticancer therapy.
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DOI：
10.1016/j.molonc.2012.01.003
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发表时间：
2012-06
影响因子：
6.6
通讯作者：
Kamitani T
中科院分区：
文献类型：
--
作者：
Tanaka T;Nakatani T;Kamitani T
肿瘤细胞可以通过上调细胞周期和逃避多种细胞应激诱导的凋亡而存活。在正常细胞中，这些生物级联反应依赖于通过泛素-蛋白酶体途径的调节蛋白的预定蛋白水解降解。因此，受调节的蛋白水解途径的中断导致异常的细胞增殖。称为SCF复合物（由Skp-1、cullin和F-box蛋白组成）或CRL（cullin-RING泛素连接酶）的泛素连接酶在E3泛素连接酶家族中占主导地位，其控制不同底物的泛素化的最后一步。在很大程度上，SCF复合物的泛素连接酶活性需要NEDD 8与cullin（即支架蛋白）缀合。本综述预计将通过几种因素（包括化合物，如MLN 4924和蛋白质分子（如COP 9信号体、Ubc 12的失活突变体和NUB 1/NUB 1 L））审查NEDD 8结合的下调系统。由于NEDD 8缀合的下调通过抑制SCF复合物的连接酶活性来影响细胞周期进程，因此NEDD 8缀合途径中的此类知识将有助于选择性抑制肿瘤发生的更宏伟的疗法。
Cancer cells can survive through the upregulation of cell cycle and the escape from apoptosis induced by numerous cellular stresses. In the normal cells, these biological cascades depend on scheduled proteolytic degradation of regulatory proteins via the ubiquitin-proteasome pathway. Therefore, interruption of regulated proteolytic pathways leads to abnormal cell-proliferation. Ubiquitin ligases called SCF complex (consisting of Skp-1, cullin, and F-box protein) or CRL (cullin-RING ubiquitin ligase) are predominant in a family of E3 ubiquitin ligases that control a final step in ubiquitination of diverse substrates. To a great extent, the ubiquitin ligase activity of the SCF complex requires the conjugation of NEDD8 to cullins, i.e. scaffold proteins. This review is anticipated to review the downregulation system of NEDD8 conjugation by several factors including a chemical compound such as MLN4924 and protein molecules (e.g. COP9 signalosome, inactive mutant of Ubc12, and NUB1/NUB1L). Since the downregulation of NEDD8 conjugation affects cell cycle progression by inhibiting the ligase activity of SCF complexes, such knowledge in the NEDD8 conjugation pathway will contribute to the more magnificent therapies that selectively suppress tumorigenesis.
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影响因子：
4.8
作者：
Amir, RE;Iwai, K;Ciechanover, A
通讯作者：
Ciechanover, A
影响因子：
4.8
作者：
Grossberger, R;Gieffers, C;Peters, JM
通讯作者：
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影响因子：
4
作者：
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通讯作者：
Chien, Cheng-Ting
影响因子：
21.3
作者：
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通讯作者：
Moon, RT
DOI：
10.1016/j.bbrc.2004.05.057
发表时间：
2004-07-02
影响因子：
3.1
作者：
Burnatowska-Hledin, MA;Kossoris, JB;Barney, CC
通讯作者：
Barney, CC