Disease relevance of Kif11

• Eg5 was highly expressed in all Philadelphia chromosome positive (Ph(+)) cell lines and BC CML patient samples [1].
• Regulation and targeting of Eg5, a mitotic motor protein in blast crisis CML: overcoming imatinib resistance [1].

High impact information on Kif11

• Treatment with Eg5 ASO produced a statistically significant reduction of tumor growth, reduction in Eg5 expression in the tumors, and changes in histone phosphorylation, consistent with a loss of Eg5 protein expression [2].
• In neurons, Eg5 is directly associated with the microtubule array and is enriched within the distal regions of developing processes [3].
• We suggest that Eg5 generates forces that help to regulate microtubule behaviors within the distal tips of developing axons and dendrites [3].
• KIFC5A knockdown partly rescues the phenotype caused by inhibition of plus-end-directed motor Eg5 by monastrol on the mitotic spindle, indicating that it is involved in the balance of forces determining bipolar spindle assembly and integrity [4].
• RanBP1-dependent centrosome splitting is specifically induced in mitosis and requires microtubule integrity and Eg5 activity [5].

Chemical compound and disease context of Kif11

• Our findings suggest that Eg5 is downstream of and regulated by Bcr-Abl tyrosine kinase in Philadelphia chromosome positive cells [1].

Biological context of Kif11

• The Knsl1 gene encoding the kinesin-related protein MmEg5 maps to mouse chromosome 19 and a related pseudogene maps to mouse chromosome 6 [6].
• The ability of monastrol to alter kinesin Eg5 and centrosome activities and spindle geometry may lead to abnormal chromosome segregation [7].
• Transient exposure to the Eg5 kinesin inhibitor monastrol leads to syntelic orientation of chromosomes and aneuploidy in mouse oocytes [7].
• Many of these analogues displayed potent inhibitory activities in the Eg5 ATPase and A2780 cell proliferation assays [8].
• Both NMR and X-ray crystallographic studies revealed that these analogues bind to an allosteric site on the Eg5 protein [8].

Associations of Kif11 with chemical compounds

• Inhibition of Eg5 expression or its activity blocks cell cycle progression and induces cell death independent of the cellular response to Imatinib [1].
• Blocking Eg5 expression with antisense oligonucleotide (Eg5-ASO) or inhibiting its activity with the small-molecule Eg5 inhibitor, S-trityl-L-cysteine induced G(2)/M cell cycle block and subsequent cell death in both Imatinib-sensitive and -resistant cells [1].

Analytical, diagnostic and therapeutic context of Kif11

• To examine the therapeutic utility of the Eg5 ASO, the compound was also evaluated in xenograft models [2].
• A conserved 21 bp siRNA was used for RNAi in both HeLa and PtK cells in which Eg5 knockdown resulted in an increased mitotic index and cells with monopolar spindles [9].
• Eg5, a microtubule-associated motor protein has been described to be highly expressed in BC CML by microarray analysis (Nowicki et al., Oncogene 2003; 22:3952-63) [1].

References