Cell Cycle and Cancer Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
J Cell Sci. 2020 May 27;133(10):jcs239723. doi: 10.1242/jcs.239723.
Centrosomes focus microtubules to promote mitotic spindle bipolarity, a critical requirement for balanced chromosome segregation. Comprehensive understanding of centrosome function and regulation requires a complete inventory of components. While many centrosome components have been identified, others yet remain undiscovered. We have used a bioinformatics approach, based on 'guilt by association' expression to identify novel mitotic components among the large group of predicted human proteins that have yet to be functionally characterized. Here, we identify chondrosarcoma-associated gene 1 protein (CSAG1) in maintaining centrosome integrity during mitosis. Depletion of CSAG1 disrupts centrosomes and leads to multipolar spindles, particularly in cells with compromised p53 function. Thus, CSAG1 may reflect a class of 'mitotic addiction' genes, whose expression is more essential in transformed cells.
中心体聚焦微管以促进有丝分裂纺锤体的两极分化,这是平衡染色体分离的关键要求。全面了解中心体的功能和调节需要完整的成分清单。虽然已经鉴定出许多中心体成分,但其他成分仍未被发现。我们使用了一种基于“关联表达”的生物信息学方法,在尚未进行功能表征的大量预测人类蛋白中识别新的有丝分裂成分。在这里,我们在维持有丝分裂过程中的中心体完整性方面鉴定出软骨肉瘤相关基因 1 蛋白(CSAG1)。CSAG1 的耗竭会破坏中心体,并导致多极纺锤体,特别是在功能受损的 p53 细胞中。因此,CSAG1 可能反映了一类“有丝分裂成瘾”基因,其表达在转化细胞中更为重要。