Department of Biochemistry and Vermont Cancer Center, University of Vermont College of Medicine, Burlington, Vermont.
J Cell Physiol. 2014 Oct;229(10):1466-74. doi: 10.1002/jcp.24588.
Core Binding Factor β (CBFβ) is complexed with the RUNX family of transcription factors in the nucleus to support activation or repression of genes related to bone (RUNX2), hematopoiesis (RUNX1) and gastrointestinal (RUNX3) development. Furthermore, RUNX proteins contribute to the onset and progression of different types of cancer. Although CBFβ localizes to cytoskeletal architecture, its biological role in the cytoplasmic compartment remains to be established. Additionally, the function and localization of CBFβ during the cell cycle are important questions relevant to its biological role. Here we show that CBFβ dynamically distributes in different stages of cell division and importantly is present during telophase at the midbody, a temporal structure important for successful cytokinesis. A functional role for CBFβ localization at the midbody is supported by striking defects in cytokinesis that include polyploidy and abscission failure following siRNA-mediated downregulation of endogenous CBFβ or overexpression of the inv(16) fusion protein CBFβ-SMMHC. Our results suggest that CBFβ retention in the midbody during cytokinesis reflects a novel function that contributes to epigenetic control.
核心结合因子 β (CBFβ) 在核内与 RUNX 家族转录因子形成复合物,以支持与骨骼(RUNX2)、造血(RUNX1)和胃肠道(RUNX3)发育相关的基因的激活或抑制。此外,RUNX 蛋白有助于不同类型癌症的发生和进展。尽管 CBFβ 定位于细胞骨架结构,但它在细胞质区室中的生物学功能仍有待确定。此外,CBFβ 在细胞周期中的功能和定位是与其生物学功能相关的重要问题。在这里,我们显示 CBFβ 在细胞分裂的不同阶段动态分布,重要的是在有丝分裂末期位于中体,这是一个对于成功胞质分裂很重要的时空调控结构。CBFβ 在中体的定位的功能作用得到了以下事实的支持:siRNA 介导的内源性 CBFβ 下调或inv(16)融合蛋白 CBFβ-SMMHC 的过表达后,胞质分裂出现明显缺陷,包括多倍体和胞质分裂失败。我们的结果表明,CBFβ 在胞质分裂过程中保留在中体中反映了一种新的功能,有助于表观遗传调控。