SPSB1 通过使 p21 不稳定来增强卵巢癌细胞的存活能力。

SPSB1 enhances ovarian cancer cell survival by destabilizing p21.

机构信息

Department of Obstetrics and Gynecology, College of Medicine, Ewha Womans University, Seoul, South Korea; Innovative Research Center for Control and Prevention of Women's Cancer, Ewha Womans University Mokdong Hospital, Seoul, South Korea.

Department of Obstetrics and Gynecology, College of Medicine, Ewha Womans University, Seoul, South Korea.

出版信息

Biochem Biophys Res Commun. 2019 Mar 12;510(3):364-369. doi: 10.1016/j.bbrc.2019.01.088. Epub 2019 Jan 31.

DOI:10.1016/j.bbrc.2019.01.088

PMID:30712944

Abstract

SPRY domain-containing SOCS box protein 1 (SPSB1) is an E3 ligase adaptor protein with unknown functions in cancer cells. In this study, we found that SPSB1 knockdown markedly decreased the viability and migration of ovarian cancer cells, while ectopic SPSB1 overexpression in IL-3-dependent Ba/F3 cells significantly increased their proliferation rate compared with empty vector-transfected cells. SPSB1 knockdown significantly elevated p21 protein and mRNA levels and induced apoptosis in ovarian cancer cells, as evidenced by increased levels of cleaved PARP and decreased levels of Bcl-2. Notably, mechanistic investigations revealed that SPSB1 accelerated p21 destabilization by directly interacting with p21 and promoting its ubiquitin-mediated proteasomal degradation. Taken together, our findings provide novel insights into the role of SPSB1 in ovarian cancer cells.

摘要

富含 SPRY 结构域的 SOCS 盒蛋白 1（SPSB1）是一种 E3 连接酶衔接蛋白，其在癌细胞中的功能未知。在这项研究中，我们发现 SPSB1 敲低显著降低了卵巢癌细胞的活力和迁移能力，而 SPSB1 过表达在 IL-3 依赖性 Ba/F3 细胞中与空载体转染细胞相比，显著增加了它们的增殖速度。SPSB1 敲低显著提高了卵巢癌细胞中 p21 蛋白和 mRNA 的水平，并诱导了细胞凋亡，这一点可以从 cleaved PARP 的水平升高和 Bcl-2 的水平降低得到证明。值得注意的是，机制研究表明，SPSB1 通过直接与 p21 相互作用并促进其泛素介导的蛋白酶体降解，加速了 p21 的不稳定。总之，我们的研究结果为 SPSB1 在卵巢癌细胞中的作用提供了新的见解。