Chromokinesins: multitalented players in mitosis

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Molecular motors generate cellular forces and act in a multitude of intracellular transport processes. The chromokinesins are a subgroup of kinesin motors. Chromokinesins act in various steps of mitosis, including chromosome condensation, metaphase alignment, chromosome segregation, cytokinesis and they help maintain genome stability. The emerging multifunctional nature of the chromokinesins provides insights into the coordination of distinct mitotic steps, and their role in maintenance of genome stability makes them attractive potential targets for therapeutic intervention.

Introduction

The equal distribution of the genome during cell division in eukaryotes is ensured by the action of a large macromolecular machine consisting of the mitotic spindle, an ensemble of cytoskeletal proteins, and numerous molecular motors, including kinesins, dyneins and myosins. Most mitotic motors are cytoplasmic during interphase and associate with the spindle during mitosis. Others associate with the kinetochores during cell division and are involved in attachment of microtubules to kinetochores, regulation of microtubule dynamics and bipolarity, chromosome movement and cytokinesis 1, 2. In addition to these spindle- and kinetochore-associated motors, members of a subgroup of kinesins are nuclear during interphase and associate with chromosome arms during cell division. These proteins are the chromokinesins [3].

Section snippets

The chromokinesins

All chromokinesins belong to either of two kinesin subfamilies: Kinesin-4 or Kinesin-10*. Kinesin-4 family members have been characterized in human, which has two different genes, KIF4A and KIF4B 4, 5, mouse [6], Xenopus 7, 8, chicken [9], Drosophila 10, 11, C. elegans [12] and plant [13]. Kinesin-10 family members have been found in human [14], Xenopus 15, 16 and Drosophila 17, 18 (Table 1). Both subfamilies

The many roles of chromokinesins in mitosis

Chromokinesins consistently localize to mitotic structures. Kinesin-4 family members associate with chromosome arms, the spindle, the central spindle and the mid-body. Kinesin-10 family members localize to chromosome arms and microtubules (Figure 1b; Table 1). Consistent with these distributions, Kinesin-4 and Kinesin-10 family members function in multiple steps of cell division.

A link between chromosome condensation and passage through mitosis

While the molecular motor activity of chromokinesins can account for their involvement in some mitotic events, such as alignment and movement of chromosomes, which directly rely on motor activity and force generation [2], several other functions such as condensation and anaphase separation of chromatids are more difficult to explain based on this motor function. A key question in understanding the complex role of chromokinesins in mitosis is whether their many effects reflect parallel and

Chromokinesins in genome stability and cancer

Chromokinesins are clearly crucial components of the mitotic machinery and are required for accurate genome segregation. Not surprisingly, loss of chromokinesin function leads to deleterious genome defects, particularly an increased number of anaphase bridges and micronuclei. The most direct evidence for a role for chromokinesins in genome stability is the observed numerical aneuploidy observed upon depletion of HKIF4A [27]. Indeed, HKIF4 was identified as a potential proto-oncogene in the

Concluding remarks

The recent functional analysis of chromokinesins has revealed that these kinesin superfamily members are crucial novel components of the mitotic machinery. Although their apparent involvement in multiple steps of mitosis at times complicates their study, the ongoing functional characterization and identification of their molecular interacting partners will undoubtedly provide novel insights into multiple aspects of mitosis. In particular, the multifunctional nature of chromokinesin action will

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