肿瘤抑制因子Rb（视网膜母细胞瘤蛋白）在约三分之一的人类肿瘤中发生突变。它抑制某些转录因子的活性，增强其他转录因子的活性，并且在体外被发现影响不同细胞系的分化。现在，Jaqueline Lees及其同事发现，在小鼠骨肉瘤模型中，在体内，Rb在决定骨细胞与棕色脂肪组织的形成之间的命运选择中扮演一个角色，通过骨头和脂肪主调控因子Runx2 和PPARgamma发挥作用。
生物谷推荐原文出处：
Nature doi:10.1038/nature09264
Rb regulates fate choice and lineage commitment in vivo
Eliezer Calo,Jose A. Quintero-Estades,Paul S. Danielian,Simona Nedelcu,Seth D. Berman" Jacqueline A. Lees
Mutation of the retinoblastoma gene (RB1) tumour suppressor occurs in one-third of all human tumours and is particularly associated with retinoblastoma and osteosarcoma1. Numerous functions have been ascribed to the product of the human RB1 gene, the retinoblastoma protein (pRb). The best known is pRb’s ability to promote cell-cycle exit through inhibition of the E2F transcription factors and the transcriptional repression of genes encoding cell-cycle regulators1. In addition, pRb has been shown in vitro to regulate several transcription factors that are master differentiation inducers2. Depending on the differentiation factor and cellular context, pRb can either suppress or promote their transcriptional activity. For example, pRb binds to Runx2 and potentiates its ability to promote osteogenic differentiation in vitro3. In contrast, pRb acts with E2F to suppress peroxisome proliferator-activated receptor γ subunit (PPAR-γ), the master activator of adipogenesis4, 5. Because osteoblasts and adipocytes can both arise from mesenchymal stem cells, these observations suggest that pRb might play a role in the choice between these two fates. However, so far, there is no evidence for this in vivo. Here we use mouse models to address this hypothesis in mesenchymal tissue development and tumorigenesis. Our data show that Rb status plays a key role in establishing fate choice between bone and brown adipose tissue in vivo.
