Runx2: A master organizer of gene transcription in developing and maturing osteoblasts
Runx2: A master organizer of gene transcription in developing and maturing osteoblasts
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DOI：
10.1002/bdrc.20043
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发表时间：
2005-09-01
影响因子：
2.1
通讯作者：
Westendorf, Jennifer J.
中科院分区：
文献类型：
--
作者：
Schroeder, Tania M.;Jensen, Eric D.;Westendorf, Jennifer J.
Runx2对于成骨细胞发育和适当的骨形成至关重要。Runx 2是转录因子Runt结构域家族的成员，它结合特异性DNA序列以调节许多基因的转录，从而控制间充质干细胞向成骨细胞的发育和成熟为骨细胞。虽然基因转录和成骨细胞发育所必需，但Runx2不足以实现最佳基因表达或骨形成。Runx2与许多蛋白质，包括转录因子和辅因子，是后期修饰，并与核基质相关联，以整合各种信号和组织成骨细胞发育和成熟过程中的关键事件。与其作为主组织者的作用一致，Runx2表达水平的改变与骨骼疾病相关。Runx2单倍不足导致锁骨颅骨发育不良，而Runx2过表达在许多骨转移癌中很常见。在这篇综述中，我们总结了Runx2通过共调节相互作用整合信号的分子机制，并讨论了其作为主组织者的作用如何根据启动子结构，发育线索和细胞环境而改变。
Runx2 is essential for osteoblast development and proper bone formation. A member of the Runt domain family of transcription factors, Runx2 binds specific DNA sequences to regulate transcription of numerous genes and thereby control osteoblast development from mesenchymal stem cells and maturation into osteocytes. Although necessary for gene transcription and osteoblast development, Runx2 is not sufficient for optimal gene expression or bone formation. Runx2 cooperates with numerous proteins, including transcription factors and cofactors, is posttranslationally modified, and associates with the nuclear matrix to integrate a variety of signals and organize crucial events during osteoblast development and maturation. Consistent with its role as a master organizer, alterations in Runx2 expression levels are associated with skeletal diseases. Runx2 haplo-insufficiency causes cleidocranial dysplasia, while Runx2 overexpression is common in many bone-metastatic cancers. In this review, we summarize the molecular mechanisms by which Runx2 integrates signals through coregulatory interactions, and discuss how its role as a master organizer may shift depending on promoter structure, developmental cues, and cellular context.