Growth/differentiation factor-5 induces growth arrest and apoptosis in mouse B lineage cells with modulation by Smad
Growth/differentiation factor-5 induces growth arrest and apoptosis in mouse B lineage cells with modulation by Smad
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DOI：
10.1016/s0898-6568(02)00088-8
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发表时间：
2003-02-01
影响因子：
4.8
通讯作者：
Nishihara, T
中科院分区：
文献类型：
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作者：
Nakahara, T;Tominaga, K;Nishihara, T
骨形态发生蛋白，包括生长/分化因子-5 (GDF-5)，是多功能细胞因子。最近对转化生长因子-p 超家族细胞内信号转导机制的研究主要集中在 Smad 蛋白上。然而，GDF-5对免疫活性细胞发挥负生长作用的机制却很少受到关注。在本研究中，我们证明GDF-5在小鼠B细胞杂交瘤HS-72细胞出现凋亡之前诱导细胞周期停滞在G1期，而HS-72细胞中Smad6和Smad7的异位表达通过消除p21（CIP-1/WAF-1）的表达和视网膜母细胞瘤蛋白的低磷酸化来抑制GDF-5诱导的G1细胞周期停滞。此外，我们发现 Smad6 和 Smad7 抑制 GDF-5 诱导的 HS-72 细胞凋亡。这些发现表明，Smad6 和 Smad7 对 B 谱系细胞中 GDF-5 介导的信号传导表现出抑制作用。 (C) 2003 Elsevier Science Inc. 保留所有权利。
Bone morphogenetic proteins, including growth/differentiation factor-5 (GDF-5), are multifunctional cytokines. Recent studies of intracellular signal transduction mechanisms for the transforming growth factor-p superfamily have focused on Smad proteins. However, scant attention has been given to the mechanism by which GDF-5 exerts its negative growth effect on immunological competent cells. In the present study, we demonstrated that GDF-5 induced cell cycle arrest in the G1 phase before the appearance of apoptosis in mouse B cell hybridoma HS-72 cells, while the ectopic expression of Smad6 and Smad7 in HS-72 cells suppressed the GDF-5-induced G1 cell cycle arrest by abolishing the expression of p21(CIP-1/WAF-1) and hypophosphorylation of retinoblastoma protein. Moreover, we found that Smad6 and Smad7 suppressed GDF-5-induced apoptosis in HS-72 cells. These findings indicated that Smad6 and Smad7 exhibit inhibitory effects toward GDF-5-mediated signaling in B lineage cells. (C) 2003 Elsevier Science Inc. All rights reserved.