The retinoblastoma protein acts as a transcriptional coactivator required for osteogenic differentiation
The retinoblastoma protein acts as a transcriptional coactivator required for osteogenic differentiation
复制标题
DOI：
10.1016/s1097-2765(01)00327-6
复制
发表时间：
2001-08-01
期刊：
影响因子：
16
通讯作者：
Hinds, PW
中科院分区：
文献类型：
--
作者：
Thomas, DM;Carty, SA;Hinds, PW
骨肉瘤的发病率增加500倍的患者谁继承突变的RB基因。为了理解为什么视网膜母细胞瘤蛋白（pRb）是骨肉瘤的特异性靶向，我们研究了它在骨生成中的功能。pRb的缺失而不是p107或p130的缺失阻断了晚期成骨细胞的分化。pRb与成骨细胞转录因子CBFA 1物理相互作用，并以CBFA 1依赖的方式与成骨细胞特异性启动子在体内结合。pRb与CBFA 1和启动子序列的关联导致成骨细胞特异性报告基因的协同反式激活。这种反式激活功能在肿瘤衍生的pRb突变体中丢失，强调了在肿瘤抑制中的潜在作用。因此，pRb的功能作为一个直接的转录辅激活因子促进成骨细胞分化，这可能有助于在骨肉瘤中的pRb的靶向。
The incidence of osteosarcoma is increased 500-fold in patients who inherit mutations in the RB gene. To understand why the retinoblastoma protein (pRb) is specifically targeted in osteosarcoma, we studied its function in osteogenesis. Loss of pRb but not p107 or p130 blocks late osteoblast differentiation. pRb physically interacts with the osteoblast transcription factor, CBFA1, and associates with osteoblast-specific, promoters in vivo in a CBFA1-dependent fashion. Association of pRb with CBFA1 and promoter sequences results in synergistic transactivation of an osteoblast-specific reporter. This transactivation function is lost in tumor-derived pRb mutants, underscoring a potential role in tumor suppression. Thus, pRb functions as a direct transcriptional coactivator promoting osteoblast differentiation, which may contribute to the targeting of pRb in osteosarcoma.