CTD Small Phosphatase Like 2 Modulates the Canonical BMP Signaling and Mesenchymal Differentiation via Smad Dephosphorylation [Cell Biology]

August 6th, 2014 by Zhao, Y., Xiao, M., Sun, B., Zhang, Z., Shen, T., Duan, X., Yu, P. B., Feng, X.-H., Lin, X.

The Bone Morphogenetic Protein (BMP) signaling pathway regulates a wide range of cellular responses in metazoans. A key step in the canonical BMP signaling is the phosphorylation and activation of transcription factors Smad1, Smad5 and Smad8 (collectively Smad1/5/8) by the type I BMP receptors. We previously identified PPM1A as a phosphatase towards dephosphorylation of all R-Smads, including Smad1/5/8. Here we report another nuclear phosphatase named SCP4/CTDSPL2, belonging to the FCP/SCP family, as a novel Smad phosphatase in the nucleus. SCP4 physically interacts with and specifically dephosphorylates Smad1/5/8, and as a result attenuates BMP-induced transcriptional responses. Knockdown of SCP4 in multipotent mesenchymal C2C12 cells leads to increased expression of BMP target genes and consequently promotes BMP-induced osteogenic differentiation. Collectively, our results demonstrate that SCP4, as a Smad phosphatase, play a critical role in BMP-induced signaling and cellular functions.