Satijn D P, Gunster M J, van der Vlag J, Hamer K M, Schul W, Alkema M J, Saurin A J, Freemont P S, van Driel R, Otte A P
E.C. Slater Institute, University of Amsterdam, The Netherlands.
Mol Cell Biol. 1997 Jul;17(7):4105-13. doi: 10.1128/MCB.17.7.4105.
The Polycomb (Pc) protein is a component of a multimeric, chromatin-associated Polycomb group (PcG) protein complex, which is involved in stable repression of gene activity. The identities of components of the PcG protein complex are largely unknown. In a two-hybrid screen with a vertebrate Pc homolog as a target, we identify the human RING1 protein as interacting with Pc. RING1 is a protein that contains the RING finger motif, a specific zinc-binding domain, which is found in many regulatory proteins. So far, the function of the RING1 protein has remained enigmatic. Here, we show that RING1 coimmunoprecipitates with a human Pc homolog, the vertebrate PcG protein BMI1, and HPH1, a human homolog of the PcG protein Polyhomeotic (Ph). Also, RING1 colocalizes with these vertebrate PcG proteins in nuclear domains of SW480 human colorectal adenocarcinoma and Saos-2 human osteosarcoma cells. Finally, we show that RING1, like Pc, is able to repress gene activity when targeted to a reporter gene. Our findings indicate that RING1 is associated with the human PcG protein complex and that RING1, like PcG proteins, can act as a transcriptional repressor.
多梳（Pc）蛋白是一种多聚体、与染色质相关的多梳家族（PcG）蛋白复合物的组成成分，该复合物参与基因活性的稳定抑制。PcG蛋白复合物的组成成分大多未知。在以脊椎动物Pc同源物为靶标的双杂交筛选中，我们鉴定出人类RING1蛋白与Pc相互作用。RING1是一种含有RING指基序的蛋白，这是一种在许多调节蛋白中都存在的特定锌结合结构域。到目前为止，RING1蛋白的功能仍然是个谜。在此，我们表明RING1与人类Pc同源物、脊椎动物PcG蛋白BMI1以及PcG蛋白多同源异型（Ph）的人类同源物HPH1共同免疫沉淀。此外，RING1在SW480人结肠直肠癌和Saos-2人骨肉瘤细胞的核结构域中与这些脊椎动物PcG蛋白共定位。最后，我们表明RING1与Pc一样，当靶向报告基因时能够抑制基因活性。我们的研究结果表明RING1与人类PcG蛋白复合物相关，并且RING1与PcG蛋白一样，可以作为转录抑制因子发挥作用。
