Search Results (2)

Centrosomes represent main microtubule organizing centers (MTOCs) in animal cells. Their duplication in S-phase enables the establishment of two MTOCs in M-phase that define the poles of the spindle and ensure equal distribution of chromosomes and centrosomes to the two daughter cells. While key functions of many centrosomal proteins have been addressed in RNAi experiments and chronic knockdown, knockout experiments with complete loss of function in all cells enable quantitative analysis of cellular phenotypes at all cell-cycle stages. Here, we show that the centriolar satellite proteins SSX2IP and WDR8 and the centriolar protein CEP135 form a complex before centrosome assembly in vertebrate oocytes and further functionally interact in somatic cells with established centrosomes. We present stable knockouts of SSX2IP, WDR8, and CEP135 in human cells. While loss of SSX2IP and WDR8 are compensated for, cep135 knockout cells display compromised PCM recruitment, reduced MTOC function, and premature centrosome splitting with imbalanced PCMs. Defective cep135 knockout centrosomes, however, manage to establish balanced spindle poles, allowing unperturbed mitosis and regular cell proliferation. Our data show essential functions of CEP135 in interphase MTOCs and demonstrate that loss of individual functions of SSX2IP, WDR8, and CEP135 are fully compensated for in mitosis. Full article

Few studies have compared gene expression in paediatric and adult acute myeloid leukaemia (AML). In this study, we have analysed mRNA-sequencing data from two publicly accessible databases: (1) National Cancer Institute’s Therapeutically Applicable Research to Generate Effective Treatments (NCI-TARGET), examining paediatric patients, and (2) The Cancer Genome Atlas (TCGA), examining adult patients with AML. With a particular focus on 144 known tumour antigens, we identified STEAP1, SAGE1, MORC4, SLC34A2 and CEACAM3 as significantly different in their expression between standard and low risk paediatric AML patient subgroups, as well as between poor and good, and intermediate and good risk adult AML patient subgroups. We found significant differences in event-free survival (EFS) in paediatric AML patients, when comparing standard and low risk subgroups, and quartile expression levels of BIRC5, MAGEF1, MELTF, STEAP1 and VGLL4. We found significant differences in EFS in adult AML patients when comparing intermediate and good, and poor and good risk adult AML patient subgroups and quartile expression levels of MORC4 and SAGE1, respectively. When examining Kyoto Encyclopedia of Genes and Genomes (KEGG) (2016) pathway data, we found that genes altered in AML were involved in key processes such as the evasion of apoptosis (BIRC5, WNT1) or the control of cell proliferation (SSX2IP, AML1-ETO). For the first time we have compared gene expression in paediatric AML patients with that of adult AML patients. This study provides unique insights into the differences and similarities in the gene expression that underlies AML, the genes that are significantly differently expressed between risk subgroups, and provides new insights into the molecular pathways involved in AML pathogenesis. Full article