Characterization of Su48, a centrosome protein essential for cell division

Abstract

The centrosome functions as the major microtubule-organizing center and plays a vital role in guiding chromosome segregation during mitosis. Centrosome abnormalities are frequently seen in a variety of cancers, suggesting that dysfunction of this organelle may contribute to malignant transformation. In our efforts to identify the protein components of the centrosome and to understand the structure features involved in the assembly and functions of this organelle, we cloned and characterized a centrosome-associated protein called Su48. We found that a coiled coil-containing subdomain of Su48 was both sufficient and required for its centrosome localization. In addition, this structure also modulates Su48 dimerization. Moreover, ectopic expression of Su48 causes abnormal mitosis, and a mutant form of Su48 disrupts the localization of ␥-tubulin to the centrosome. Finally, by microinjection of an anti-Su48 antibody, we found that disruption of normal Su48 functions leads to mitotic failure, possibly due to centrosome defects or incomplete cytokinesis. Thus, Su48 represents a previously unrecognized centrosome protein that is essential for cell division. We speculate that Su48 abnormalities may cause aberrant chromosome segregation and may contribute to aneuploidy and malignant transformation.cancer ͉ coiled coil ͉ mitosis

ZNF365 Promotes Stability of Fragile Sites and Telomeres

“…A previous study reported that misexpression of ZNF365 led to cytokinesis failure, suggesting that its deregulation may contribute to the development of genomic instability during tumorigenesis [46]. Of high relevance to our findings, recent genome-wide association studies have identified SNPs within ZNF365 that bear significant correlation with breast cancer susceptibility [47].…”

Lats2 Is an Essential Mitotic Regulator Required for the Coordination of Cell Division

“…Regulation of Cytokinesis by Lats2-Recently, it has been reported that a number of novel centrosomal proteins such as Cep55 and Su48 regulate cytokinesis in mammalian cells (81,82). We have shown here that, like these centrosomal proteins, the centrosomal protein Lats2 localizes at the midbody during late mitosis and plays a role in cytokinesis.…”

Genetic polymorphisms and breast cancer risk: evidence from meta-analyses, pooled analyses, and genome-wide association studies

“…This gene has a complex pattern of alternative splicing and transcriptional start sites [137]. Wang et al [138] found that ZNF365A localizes to the centrosome throughout the cell cycle in several human cell lines. A mutation analysis demonstrated that the centrosomal localization of ZNF365A requires 2 coiled-coil subdomains but not the C-terminal zinc finger structure.…”