Calcineurin regulates phosphorylation status of transcription factor osterix.
Calcineurin regulates phosphorylation status of transcription factor osterix.
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DOI：
10.1016/j.bbrc.2008.12.094
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发表时间：
2009-02
影响因子：
3.1
通讯作者：
H. Okamura;B. Amorim;Jie Wang;Kaya Yoshida;T. Haneji
中科院分区：
文献类型：
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作者：
H. Okamura;B. Amorim;Jie Wang;Kaya Yoshida;T. Haneji
Osterix是一种成骨细胞特异性转录因子，对成骨细胞分化和骨形成至关重要。钙调磷酸酶通过调节成骨细胞分化调节骨形成。然而，骨甾体的翻译后修饰，如磷酸化和骨甾体与钙调磷酸酶之间的相互作用尚不清楚。在本研究中，我们通过免疫沉淀法和Western分析法证实了钙调磷酸酶与骨质体的相互作用。免疫细胞化学研究还发现骨甾体和钙调磷酸酶在细胞核内共定位。骨甾分子上钙调磷酸酶结合基序的缺失破坏了骨甾-钙调磷酸酶的相互作用。磷酸酶抑制剂FK506和calyculin a可以增强骨甾体的磷酸化状态，而重组钙调磷酸酶则可以降低骨甾体的磷酸化状态。我们目前的研究表明，钙调磷酸酶通过其磷酸化修饰在骨细胞的功能中起重要作用。
Osterix is an osteoblast-specific transcriptional factor that is essential for osteoblast differentiation and bone formation. Calcineurin regulates bone formation through modulating osteoblast differentiation. However, post-translational modification of osterix such as phosphorylation and interactions between osterix and calcineurin remains unclear. In the present study, we demonstrated that calcineurin interacted with osterix determined by immunoprecipitation assay and Western analysis. Immunocytochemical study also revealed that osterix and calcineurin were co-localized in nucleus. Deletion of calcineurin binding motif on osterix molecule disrupted osterix–calcineurin interaction. Phosphorylation status of osterix was augmented by treatment with phosphatase inhibitors, FK506 and calyculin A. In contrast, treatment of recombinant calcineurin reduced phosphorylation status of osterix. Our present study suggests that calcineurin has an important role in the function of osterix through its modification of phosphorylation.