SENP1 inhibition induces apoptosis and growth arrest of multiple myeloma cells through modulation of NF-κB signaling
SENP1 inhibition induces apoptosis and growth arrest of multiple myeloma cells through modulation of NF-κB signaling
复制标题
SENP1 抑制通过调节 NF-kappaB 信号传导诱导多发性骨髓瘤细胞凋亡和生长停滞。
DOI：
10.1016/j.bbrc.2015.03.047
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发表时间：
2015-05-01
影响因子：
3.1
通讯作者：
Wang, Li-Sheng
中科院分区：
文献类型：
--
作者：
Xu, Jun;Sun, Hui-Yan;Wang, Li-Sheng
SUMO/sentrin特异性蛋白酶1（Senp 1）是蛋白质类小泛素化的重要调控蛋白，影响细胞周期、增殖和分化。Senp 1介导的蛋白去糖基化在多发性骨髓瘤病理生理进展中的作用尚不清楚。在这项研究中，我们证明了Senp 1在多发性骨髓瘤细胞中过表达并被IL-6诱导。慢病毒介导的Senp 1敲低触发MM细胞凋亡并降低MM细胞的活力、增殖和集落形成能力。NF-κ B家族成员包括P65和抑制蛋白Ik B α在调节MM细胞存活和增殖中起重要作用。我们进一步证实，Senp 1抑制降低了IL-6诱导的P65和Ik B α磷酸化，导致MM细胞中NF-κ B信号转导的失活。这些结果描述了Senp 1在IL-6诱导的MM细胞增殖和存活中的关键作用，表明其可能是MM的潜在新治疗靶点。All rights reserved.
SUMO/sentrin specific protease 1 (Senp1) is an important regulation protease in the protein sumoylation, which affects the cell cycle, proliferation and differentiation. The role of Senp1 mediated protein desumoylation in pathophysiological progression of multiple myeloma is unknown. In this study, we demonstrated that Senp1 is overexpressed and induced by IL-6 in multiple myeloma cells. Lentivirus-mediated Senp1 knockdown triggers apoptosis and reduces viability, proliferation and colony forming ability of MM cells. The NF-kappa B family members including P65 and inhibitor protein IkB alpha play important roles in regulation of MM cell survival and proliferation. We further demonstrated that Senp1 inhibition decreased IL-6-induced P65 and IkB alpha phosphorylation, leading to inactivation of NF-kappa B signaling in MM cells. These results delineate a key role for Senp1 in IL-6 induced proliferation and survival of MM cells, suggesting it may be a potential new therapeutic target in MM. (C) 2015 Elsevier Inc. All rights reserved.