Breast cancer-associated gene 3 interacts with Rac1 and augments NF-κB signaling in vitro, but has no effect on RANKL-induced bone resorption in vivo
Breast cancer-associated gene 3 interacts with Rac1 and augments NF-κB signaling in vitro, but has no effect on RANKL-induced bone resorption in vivo
复制标题
乳腺癌相关基因 3 与 Rac1 相互作用并在体外增强 NF-kappa B 信号传导，但对体内 RANKL 诱导的骨吸收没有影响
DOI：
10.3892/ijmm.2017.3091
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发表时间：
2017-10-01
影响因子：
5.4
通讯作者：
Insogna, Karl
中科院分区：
文献类型：
--
作者：
Yao, Chen;Yu, Kuan-Ping;Insogna, Karl
乳腺癌相关基因3（BCA3）是最近发现的一种衔接蛋白，其功能尚不清楚。BCA 3已被报道是核因子-κ B（NF-κ B）信号传导的重要调节剂。据报道，它还与小的GTdR，Rac 1相互作用。与该观察结果一致，在本研究中，发现BCA 3与293细胞中的核Rac 1相互作用并影响NF-κ B信号传导。另外的实验显示，根据细胞类型，BCA 3在体外增强、减弱或不影响NF-κ B信号传导。由于经典NF-κ B信号传导是成熟破骨细胞形成和功能所需的活化核因子-κ B受体激活剂（RANK）的关键下游靶标，因此使用组织蛋白酶K启动子在体内破骨细胞中选择性过表达BCA 3，并检查了对外源性核因子-κ B受体激活剂配体（RANKL）给药的反应。尽管其能够增强其他细胞中的NF-κ B信号传导，但注射高剂量RANKL的转基因动物与其野生型同窝动物具有相同的高钙反应。此外，2周低剂量RANKL输注诱导的骨丢失程度在两组中相同。结合早期的研究，我们的研究数据表明，BCA 3可以影响NF-κ B B信号转导，并且BCA 3在此过程中发挥细胞类型依赖性作用。BCA 3/NF-κ B相互作用在体内骨中的意义仍有待确定。
Breast cancer-associated gene 3 (BCA3) is a recently identified adaptor protein whose functions are still being defined. BCA3 has been reported to be an important regulator of nuclear factor-kappa B (NF-kappa B) signaling. It has also been reported to interact with the small GTPase, Rac1. Consistent with that observation, in the present study, BCA3 was found to interact with nuclear Rac1 in 293 cells and influence NF-kappa B signaling. Additional experiments revealed that depending on cell type, BCA3 augmented, attenuated or had no effect on NF-kappa B signaling in vitro. Since canonical NF-kappa B signaling is a critical downstream target from activated receptor activator of nuclear factor-kappa B (RANK) that is required for mature osteoclast formation and function, BCA3 was selectively overexpressed in osteoclasts in vivo using the cathepsin K promoter and the response to exogenous receptor activator of nuclear factor-kappa B ligand (RANKL) administration was examined. Despite its ability to augment NF-kappa B signaling in other cells, transgenic animals injected with high-dose RANKL had the same hypercalcemic response as their wild-type littermates. Furthermore, the degree of bone loss induced by a 2-week infusion of low-dose RANKL was the same in both groups. Combined with earlier studies, the data from our study data indicate that BCA3 can affect NF-kappa B signaling and that BCA3 plays a cell-type dependent role in this process. The significance of the BCA3/NF-kappa B interaction in vivo in bone remains to be determined.