Ski represses bone morphogenic protein signaling in Xenopus and mammalian cells.
Ski represses bone morphogenic protein signaling in Xenopus and mammalian cells.
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DOI：
10.1073/pnas.97.26.14394
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发表时间：
2000-12
影响因子：
11.1
通讯作者：
W. Wang;F. V. Mariani;R. Harland;K. Luo
中科院分区：
文献类型：
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作者：
W. Wang;F. V. Mariani;R. Harland;K. Luo
骨形态发生蛋白（BMPs）在脊椎动物的发育过程中起着重要的作用。在非洲爪蟾中，BMP作为表皮诱导剂，也作为神经发生的负调节剂。BMP信号传导的拮抗导致神经化。BMP通过细胞表面受体和下游Smad分子发出信号。在用BMP刺激后，Smad 1、Smad 5和Smad 8被活化的BMP受体磷酸化，与Smad 4形成复合物，并易位到细胞核中，在那里它们调节BMP靶基因的表达。在这里，我们表明，Ski癌蛋白可以阻止BMP信号和BMP反应基因在非洲爪蟾和哺乳动物细胞中的表达，通过直接相互作用和抑制BMP特异性Smad复合物的活性。这种拮抗BMP信号传导的能力导致在非洲爪蟾胚胎中Ski的神经化和鼠W-20-17细胞的成骨细胞分化的阻断。因此，Ski能够抑制所有受体相关Smads的活性，并可能通过调节转化生长因子β家族成员的信号传导活性来调节脊椎动物的发育。
The bone morphogenic proteins (BMPs) play important roles in vertebrate development. In Xenopus, BMPs act as epidermal inducers and also as negative regulators of neurogenesis. Antagonism of BMP signaling results in neuralization. BMPs signal through the cell-surface receptors and downstream Smad molecules. Upon stimulation with BMP, Smad1, Smad5, and Smad8 are phosphorylated by the activated BMP receptors, form a complex with Smad4, and translocate into the nucleus, where they regulate the expression of BMP target genes. Here, we show that the Ski oncoprotein can block BMP signaling and the expression of BMP-responsive genes in both Xenopus and mammalian cells by directly interacting with and repressing the activity of BMP-specific Smad complexes. This ability to antagonize BMP signaling results in neuralization by Ski in the Xenopus embryo and blocking of osteoblast differentiation of murine W-20-17 cells. Thus, Ski is able to repress the activity of all receptor-associated Smads and may regulate vertebrate development by modulating the signaling activity of transforming growth factor-beta family members.