p68 (Ddx5) interacts with Runx2 and regulates osteoblast differentiation
p68 (Ddx5) interacts with Runx2 and regulates osteoblast differentiation
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DOI：
10.1002/jcb.21526
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发表时间：
2008-04-01
影响因子：
4
通讯作者：
Westendorf, Jennifer J.
中科院分区：
文献类型：
--
作者：
Jensen, Eric D.;Niu, Lingling;Westendorf, Jennifer J.
Runx2 是间充质祖细胞成骨细胞发育的重要转录因子。 Runx2 通过与众多转录因子和共激活因子相互作用以整合细胞核内的信号事件来调节基因表达。在这项研究中，我们使用亲和纯化和蛋白质组技术来鉴定新型 Runx2 相互作用蛋白。其中一种蛋白质是 DEAD box RNA 解旋酶 p68 (Ddx5)。 p68 调节 RNA 表达的许多方面，包括转录和剪接。 p68 与 Runx2 共定位于细胞核内的点状病灶中。在转录测定中，p68 充当 Runx2 的共激活子，但其解旋酶活性对于共激活并不是必需的。相应地，Runx2 转录活性在 p68 抑制的细胞中被减弱。令人惊讶的是，多能祖细胞 C2C12 细胞系的成骨细胞分化通过 p68 抑制而加速，并且 Runx2 抑制颅骨祖细胞中 p68 的表达。这些数据共同证明p68是Runx2的新型共激活剂，但它抑制祖细胞的成骨分化。此外，Runx2 在调节成骨细胞前体中的 p68 水平方面发挥着积极作用。因此，Runx2 和 p68 之间的串扰在多个水平上控制成骨细胞的规格和成熟。
Runx2 is an essential transcription factor for osteoblast development from mesenchymal progenitors. Runx2 regulates gene expression by interacting with numerous transcription factors and co-activators to integrate signaling events within the nucleus. In this study we used affinity purification and proteomic techniques to identify novel Runx2 interacting proteins. One of these proteins is the DEAD box RNA helicase, p68 (Ddx5). p68 regulates many aspects of RNA expression, including transcription and splicing. p68 co-localized with Runx2 in punctate foci within the nucleus. In transcription assays, p68 functioned as a co-activator of Runx2, but its helicase activity was not essential for coactivation. In accordance, Runx2 transcriptional activity was muted in p68-suppressed cells. Surprisingly, osteoblast differentiation of the multipotent progenitor C2C12 cell line was accelerated by p68 suppression and Runx2 suppressed p68 expression in calvarial progenitor cells. Together these data demonstrate that p68 is a novel co-activator for Runx2, but it inhibits osteogenic differentiation of progenitor cells. Moreover Runx2 has an active role in regulating p68 levels in osteoblast precursors. Thus, crosstalk between Runx2 and p68 controls osteoblast specification and maturation at multiple levels.