During mitosis, chromosomes establish connections to mitotic spindle microtubules (MTs) via specialized protein complexes, called kinetochores, and subsequently translocate to the midzone of the bipolar spindle. This process is known as “congression”, and is dynamic in nature: the chromosomes are constantly moving in an oscillatory pattern, with paired chromosomes displaying coordinated movements. Proper mitotic chromosome alignment is highly dependent on the activity of kinesin-8 motors, including Kif18A (EC[1],[2]. Although the molecular process is not yet elucidated, proof was found that Kif18A is a motile microtubule depolymerase essential for chromosome congression[3], and controls the persistent movement of chromosomes by both increasing the rate at which they make directional switches and slowing the velocity of their movement. Moreover, it is hypothesized that Kif18A forms a gradient along kinetochore-microtubules (kMTs) that directly regulates their length and dynamics to facilitate chromosome alignment at the spindle equator[4].

Kinesins listed: Kif18AKSP

[1] J. Stumpff et al. Kif18A and chromokinesins confine centromere movements via microtubule growth suppression and spatial control of kinetochore tension. Dev Cell. 2012 May 15;22(5):1017-29.
[2] J. Braun et al. Synthesis and Biological Evaluation of Optimized Inhibitors of the Mitotic Kinesin Kif18A. ACS Chem Biol. 2015 Feb 20;10(2):554-60.
[3] M.I. Mayr et al. The human kinesin Kif18A is a motile microtubule depolymerase essential for chromosome congression. Curr Biol. 2007 Mar 20;17(6):488-98.
[4] J. Stumpff et al. The kinesin-8 motor Kif18A suppresses kinetochore movements to control mitotic chromosome alignment. Dev Cell. 2008 Feb;14(2):252-62.

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2407 BTB 1 The first small molecule reversible inhibitor of the mitotic motor protein Kif18A €70.00

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