Disease relevance of CKAP5

• TACC1-chTOG-Aurora A protein complex in breast cancer [1].
• The level of the expression of ch-TOG transcripts was also studied in the various differentiation stages of the human colonic adenocarcinoma cell line Caco-2 [2].
• We recently reported on the over-expression of a new gene, colonic and hepatic tumor over-expressed gene (ch-TOG) in human hepatomas and colonic tumors [3].
• In the present study, we demonstrate the expression of ch-TOG mRNA in human brain tumors as well as in numerous areas of healthy human and baboon brain [3].

High impact information on CKAP5

• In TACC3-depleted cells, spindles are well organized, but microtubules are partially destabilized and ch-TOG is no longer concentrated on spindle microtubules [4].
• The common feature of proteins in this family is the presence of HEAT repeat-containing TOG domains near the NH2 terminus [5].
• A functional overlap with TOGp, a MT regulator known to counteract MCAK, was suggested by similar CaMKIIgamma- and TOGp-depletion phenotypes, namely disorganized multipolar spindles [6].
• The second phenotype involves TOGp-dependent counteraction of excessive MCAK activity during mitosis, which recapitulates the previously established plus-end specific counteractive activities in vitro [7].
• The first involves a role for TOGp in protecting spindle MTs from MCAK activity at the centrosome, which appears essential to prevent the formation of disorganized multipolar spindles [7].

Biological context of CKAP5

• Using siRNAs, we further show that depletion of chTOG and, to a lesser extent of TACC1, perturbates cell division [1].
• Here we extensively depleted TACC3 and ch-TOG from HeLa cells using RNA interference [4].
• The major functions of TOGp during mitosis are to focus MT minus ends at spindle poles, maintain centrosome integrity, and contribute to spindle bipolarity [8].
• Hybridization analyses on Southern blot and on metaphase chromosomes indicate that this gene is present as a single copy in the genome and is localized on the short arm of chromosome 11. ch-TOG transcripts are present in several human tissues [2].
• The third involves an unexpected destabilization of the interphase MTs by overexpressed TOGp, a phenotype that requires endogenous MCAK [7].

Anatomical context of CKAP5

• We propose that TACC proteins, which we also named 'Taxins', control mRNA translation and cell division in conjunction with microtubule organization and in association with chTOG and Aurora A, and that these complexes and cell processes may be affected during mammary gland oncogenesis [1].
• TOGp, the human homolog of XMAP215/Dis1, is required for centrosome integrity, spindle pole organization, and bipolar spindle assembly [8].
• TOG2, the large protein isoform of TOG, is the only isoform detected in oligodendrocytes in culture [9].
• To understand how TOGp interacts with the microtubule lattice, we cloned full-length TOGp and various truncations for expression in a reticulocyte lysate system [10].
• In this study, we report that another ubiquitous MAP, TOG in human and its homologue in Xenopus XMAP215, associates also with p34cdc2 kinase and directs it to the microtubule cytoskeleton [11].

Analytical, diagnostic and therapeutic context of CKAP5

• A cDNA clone of 6.449 kb ch-TOG (for colonic and hepatic tumor over-expressed gene) initially selected from various human libraries and completed by 5' rapid amplification of cDNA ends (RACE) PCR is described [2].
• Immunofluorescence microscopy using affinity-purified TOGp antibodies revealed that the distribution of TOGp was dependent upon the cell cycle [12].
• Finally, we demonstrated interaction between TOG/XMAP215 and cyclin B1 by co-immunoprecipitation assays [11].
• Training produced a significant improvement in chair sit and reach, arm curl, chair stand and 6 min walk test scores in the TYOG and TOG when they were compared to the control groups (p<0.05) [13].

References