Hsu L C, White R L
Huntsman Cancer Institute, University of Utah, 15 N 2030 E, Room 7480, Salt Lake City, UT 84112, USA.
Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):12983-8. doi: 10.1073/pnas.95.22.12983.
Centrosomes and their associated microtubules direct events during mitosis and control the organization of animal cell structures and movement during interphase. The centrosome replicates during the cell cycle, directs the assembly of bipolar mitotic spindles, and plays an important role in maintaining the fidelity of cell division. Recently, tumor suppressors such as p53 and retinoblastoma protein pRB have been localized to the centrosome in a cell cycle-dependent manner. Immunofluorescence microscopy and analysis of isolated centrosomes now provide evidence that BRCA1 protein, a suppressor of tumorigenesis in breast and ovary, also is associated with centrosomes during mitosis. Our results indicate that BRCA1 localizes with the centrosome during mitosis and coimmunoprecipitates with gamma-tubulin, a centrosomal component essential for nucleation of microtubules. Furthermore, gamma-tubulin associates preferentially with a hypophosphorylated form of BRCA1.
中心体及其相关微管在有丝分裂期间指导细胞活动,并在间期控制动物细胞结构的组织和运动。中心体在细胞周期中进行复制,指导双极有丝分裂纺锤体的组装,并在维持细胞分裂的准确性方面发挥重要作用。最近,诸如p53和视网膜母细胞瘤蛋白pRB等肿瘤抑制因子已以细胞周期依赖性方式定位于中心体。免疫荧光显微镜检查和对分离出的中心体的分析现在提供了证据,表明乳腺癌和卵巢癌肿瘤发生的抑制因子BRCA1蛋白在有丝分裂期间也与中心体相关。我们的结果表明,BRCA1在有丝分裂期间定位于中心体,并与γ-微管蛋白共免疫沉淀,γ-微管蛋白是微管成核所必需的中心体成分。此外,γ-微管蛋白优先与BRCA1的低磷酸化形式结合。