Increased Cul1 expression promotes melanoma cell proliferation through regulating p27 expression
Increased Cul1 expression promotes melanoma cell proliferation through regulating p27 expression
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DOI：
10.3892/ijo_00000786
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发表时间：
2010-11-01
影响因子：
5.2
通讯作者：
Li, Gang
中科院分区：
文献类型：
--
作者：
Chen, Guangdi;Li, Gang
Cullin 1（Cul 1）是最大的泛素-蛋白E3连接酶家族SCE（Skp 1/Cullin/Rbx 1/F-box protein）复合物的刚性支架，其异常表达与SCF E3连接酶功能障碍有关。以前，我们发现Cul 1的表达在黑色素瘤的早期阶段增加。在本研究中，我们进一步研究了Cul 1在黑色素瘤发展中的作用。我们的研究结果表明，Cul 1的敲低抑制黑色素瘤细胞的生长，而Cul 1的过表达通过控制细胞周期进程增强细胞增殖。我们还发现Cul 1通过功能性SCFSkp 2复合物降解p27来调节黑色素瘤细胞的生长和细胞周期进程。这项研究阐明了Cul 1在黑色素瘤细胞增殖中的作用，并提高了我们对Cul 1在黑色素瘤早期表达增加的理解。
Cullin1 (Cul1) serves as a rigid scaffold in SCE (Skp1/Cullin/Rbx1/F-box protein) complex, the largest family of ubiquitin-protein E3 ligases, and aberrant expression of Cul1 is involved in dysfunction of SCF E3 ligases. Previously, we found that Cul1 expression is increased in early stages of melanoma. In the present study, we further investigated the role of Cul1 in melanoma development. Our results showed that knockdown of Cul1 inhibits melanoma cell growth while overexpression of Cul1 enhances cell proliferation through the control of cell cycle progression. We also found that Cul1 regulates melanoma cell growth and cell cycle progression through degradation of p27 by functional SCFSkp2 complex. This study elucidates the role of Cul1 in melanoma cell proliferation and improves our understanding of increased expression of Cul1 in early stages of melanoma.