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Cul1 表达增加通过调节 p27 表达促进黑素瘤细胞增殖。

Increased Cul1 expression promotes melanoma cell proliferation through regulating p27 expression.

机构信息

Department of Dermatology and Skin Science, Jack Bell Research Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, BC V6H 3Z6, Canada.

出版信息

Int J Oncol. 2010 Nov;37(5):1339-44. doi: 10.3892/ijo_00000786.

Abstract

Cullin1 (Cul1) serves as a rigid scaffold in SCF (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.

摘要

Cullin1 (Cul1) 作为 SCF(Skp1/Cullin/Rbx1/F-box protein)复合物的刚性支架,是最大的泛素蛋白 E3 连接酶家族之一,Cul1 的异常表达与 SCF E3 连接酶功能障碍有关。此前,我们发现 Cul1 在黑色素瘤的早期阶段表达增加。在本研究中,我们进一步研究了 Cul1 在黑色素瘤发展中的作用。结果表明,敲低 Cul1 可抑制黑色素瘤细胞生长,而过表达 Cul1 通过控制细胞周期进程增强细胞增殖。我们还发现 Cul1 通过功能性 SCFSkp2 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 Cul1 在黑色素瘤细胞增殖中的作用,加深了我们对黑色素瘤早期 Cul1 高表达的认识。

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