subito: Biological Overview | Evolutionary Homologs | Developmental Biology | Effects of Mutation | References
Gene name - subito

Synonyms -

Cytological map position - 54E7

Function - cytoskeleton

Keywords - meiotic spindle organization and biogenesis, mitosis

Symbol - sub

FlyBase ID: FBgn0003545

Genetic map position - 2-86

Classification - kinesin

Cellular location - cytoplasmic

NCBI link: Entrez Gene
sub orthologs: Biolitmine
Recent literature
Das, A., Shah, S. J., Fan, B., Paik, D., DiSanto, D. J., Hinman, A. M., Cesario, J. M., Battaglia, R. A., Demos, N. and McKim, K. S. (2015). Spindle assembly and chromosome segregation requires central spindle proteins in Drosophila oocytes. Genetics [Epub ahead of print]. PubMed ID: 26564158
Oocytes segregate chromosomes in the absence of centrosomes. In this situation, the chromosomes direct spindle assembly. It is still unclear in this system, what factors are required for homologous chromosome bi-orientation and spindle assembly. The Drosophila kinesin-6 protein Subito, though non-essential for mitotic spindle assembly, is required to organize a bipolar meiotic spindle and chromosome bi-orientation in oocytes. Along with the chromosomal passenger complex (CPC), Subito is an important part of the metaphase I central spindle. This study consisted of genetic screens to identify genes that interact with subito or the CPC component Incenp. In addition, the meiotic mutant phenotype for some of the genes identified in these screens were characterized. Use of a heat shock inducible system showed that the Centralspindlin component RacGAP50C and downstream regulators of cytokinesis Rho1, Sticky and RhoGEF2, are required for homologous chromosome bi-orientation in metaphase I oocytes. This suggests a novel function for proteins normally involved in mitotic cell division, in the regulation of microtubule-chromosome interactions. The kinetochore protein, Polo kinase, was also shown to be required for maintaining chromosome alignment and spindle organization in metaphase I oocytes. In combination these results support a model where the meiotic central spindle and associated proteins are essential for acentrosomal chromosome segregation.
Ye, A. A., Torabi, J. and Maresca, T. J. (2016). Aurora A kinase amplifies a midzone phosphorylation gradient to promote high-fidelity cytokinesis. Biol Bull 231: 61-72. PubMed ID: 27638695
During cytokinesis, aurora B kinase (ABK) relocalizes from centromeres to the spindle midzone, where it is thought to provide a spatial cue for cytokinesis. While global ABK inhibition in Drosophila S2 cells results in macro- and multi-nucleated large cells, mislocalization of midzone ABK (mABK) by depletion of Subito (Drosophila MKLP2) does not cause notable cytokinesis defects. Subito depletion was, therefore, used to investigate the contribution of other molecules to cytokinesis in the absence of mABK. Inhibiting potential polar relaxation pathways via removal of centrosomes (CNN RNAi) or a kinetochore-based phosphatase gradient (Sds22 RNAi) did not result in cytokinesis defects on their own or in combination with loss of mABK. Disruption of aurora A kinase (AAK) activity resulted in midzone assembly defects, but did not significantly affect contractile ring positioning or cytokinesis. Live-cell imaging of an aurora kinase phosphorylation sensor revealed that midzone substrates were less phosphorylated in AAK-inhibited cells, despite the fact that midzone levels of active phosphorylated ABK (pABK) were normal. The data suggest that equatorial stimulation rather than polar relaxation mechanisms is the major determinant of contractile ring positioning and high-fidelity cytokinesis in Drosophila S2 cells. Furthermore, it is proposed that equatorial stimulation is mediated primarily by the delivery of factors to the cortex by noncentrosomal microtubules (MTs), as well as a midzone-derived phosphorylation gradient that is amplified by the concerted activities of mABK and a soluble pool of AAK.
Das, A., Cesario, J., Hinman, A. M., Jang, J. K. and McKim, K. S. (2018). Kinesin 6 regulation in Drosophila female meiosis by the non-conserved N- and C-terminal domains. G3 (Bethesda). PubMed ID: 29514846
Bipolar spindle assembly occurs in the absence of centrosomes in the oocytes of most organisms. In the absence of centrosomes in Drosophila oocytes, it has been proposed proposed that the kinesin 6 Subito, a MKLP-2 homolog, is required for establishing spindle bipolarity and chromosome biorientation by assembling a robust central spindle during prometaphase I. Although the functions of the conserved motor domains of kinesins is well studied, less is known about the contribution of the poorly conserved N- and C- terminal domains to motor function. This study has investigated the contribution of these domains to kinesin 6 functions in meiosis and early embryonic development. The N-terminal domain has antagonistic elements that regulate localization of the motor to microtubules. Other parts of the N- and C- terminal domains are not required for microtubule localization but are required for motor function. Some of these elements of Subito are more important for either mitosis or meiosis, as revealed by separation-of-function mutants. One of the functions for both the N- and C-terminals domains is to restrict the CPC to the central spindle in a ring around the chromosomes. Evidence is provided that CDK1 phosphorylation of Subito regulates its activity associated with homolog bi-orientation. These results suggest the N- and C-terminal domains of Subito, while not required for localization to the central spindle microtubules, have important roles regulating Subito, by interacting with other spindle proteins and promoting activities such as bipolar spindle formation and homologous chromosome bi-orientation during meiosis.
Rome, P. and Ohkura, H. (2018). A novel microtubule nucleation pathway for meiotic spindle assembly in oocytes. J Cell Biol. PubMed ID: 30087124
The meiotic spindle in oocytes is assembled in the absence of centrosomes, the major microtubule nucleation sites in mitotic and male meiotic cells. A crucial, yet unresolved question in meiosis is how spindle microtubules are generated without centrosomes and only around chromosomes in the exceptionally large volume of oocytes. This study reports a novel oocyte-specific microtubule nucleation pathway that is essential for assembling most spindle microtubules complementarily with the Augmin pathway. This pathway is mediated by the kinesin-6 Subito/MKlp2, which recruits the gamma-tubulin complex to the spindle equator to nucleate microtubules in Drosophila oocytes. Away from chromosomes, Subito interaction with the gamma-tubulin complex is suppressed by its N-terminal region to prevent ectopic microtubule assembly in oocytes. It was further demonstrated in vitro that the Subito complex from ovaries can nucleate microtubules from pure tubulin dimers. Collectively, microtubule nucleation regulated by Subito drives spatially restricted spindle assembly in oocytes.

In the oocytes of many species, bipolar spindles form in the absence of centrosomes. Drosophila oocyte chromosomes have a major role in nucleating microtubules, a process that precedes the bundling and assembly of these microtubules into a bipolar spindle. Evidence is presented that a region similar to the anaphase central spindle functions to organize acentrosomal spindles. subito mutants are characterized by the formation of tripolar or monopolar spindles and nondisjunction of homologous chromosomes at meiosis I. subito encodes a kinesinlike protein and associates with the meiotic central spindle, consistent with its classification in the Kinesin 6/MKLP1 family. This class of proteins is known to be required for cytokinesis, but the current results suggest a new function in spindle formation. The meiotic central spindle appears during prometaphase and includes passenger complex proteins such as AurB and Inner centromere protein (Incenp). Unlike mitotic cells, the passenger proteins do not associate with centromeres before anaphase. In the absence of Subito, central spindle formation is defective and AurB and Incenp fail to properly localize. It is proposed that Subito is required for establishing and/or maintaining the central spindle in Drosophila oocytes, and this substitutes for the role of centrosomes in organizing the bipolar spindle (Jang, 2005).

In the acentrosomal pathway for spindle formation, that functions in the oocytes of many animals, the chromosomes trigger spindle formation by capturing free microtubules that are present in the cytoplasm. These microtubules are then bundled and sorted to generate two poles in a process that involves a variety of motor protein-microtubule interactions. Plus-end-directed motors of the BimC class such as Eg5 are proposed to generate bundles of antiparallel microtubules, an activity that could be important for promoting the formation of bipolar instead of monopolar spindles. Minus-end-directed motors such as kinesins in the C-terminal motor class or dynein have been proposed to bundle parallel microtubules and taper them into defined poles (Jang, 2005 and references therein).

Although the activities of a variety of motors has been studied in such systems as Xenopus extracts, the formation of acentrosomal spindles in vivo is still poorly understood. Although Drosophila female meiosis is an excellent system to study acentrosomal spindle formation, the only motor protein with a role in spindle assembly that has been extensively studied is NCD, a C-terminal motor kinesin. Consistent with a role in focusing the poles, ncd mutant spindles are frequently multipolar or apolar (Hatsumi, 1992; Matthies, 1996). Nonmotor proteins have also been shown to make important contributions to Drosophila acentrosomal spindle organization. For example, spindle pole-associated proteins TACC and MSPS have a role in bipolar spindle pole formation (Cullen, 2001). The AXS protein is present within a structure ensheathing the meiotic spindle and has a role in meiotic spindle assembly (Kramer, 2003). These studies suggest there are important proteins or structures that modulate the interaction of motors and microtubules in acentrosomal spindle assembly (Jang, 2005 and references therein).

Previous studies in Drosophila oocytes have suggested that the process of acentrosomal spindle formation is initiated by the capture of free microtubules by the chromosomes followed by bundling and sorting of microtubules by minus-end-directed motors and the accumulation of certain proteins at the spindle poles (Matthies, 1996; Cullen, 2001). The role of the subito (sub) gene in acentrosomal spindle formation has been investigated. sub encodes a kinesinlike protein whose sequence is most similar to the MKLP1 (mitotic kinesin like protein 1) family (Giunta, 2002) (now Kinesin 6, Dagenbach, 2004). Mutants in sub have a phenotype consistent with a role in organizing the bipolar spindle. Female meiosis in sub mutants (Giunta, 2002) is characterized by the formation of monopolar and tripolar spindles and the nondisjunction of homologous chromosomes during the first meiotic division (Jang, 2005).

This study shows that Sub protein is bound to the meiotic central spindle, a pattern that is consistent with its assignment to the MKLP1 class of proteins. Sub and the central spindle appear at the earliest stages of prometaphase, before bipolar spindle formation. Indeed, Sub is required for assembly of the central spindle. It is suggested that the precocious assembly of the central spindle has a primary role in organizing the meiotic spindle in the absence of centrosomes (Jang, 2005).

These results suggest that the kinesinlike protein Subito has an important role in Drosophila acentrosomal spindle formation, possibly by organizing the prominent central spindle that assembles at meiotic prometaphase. Interestingly, Sub has several characteristics similar to MKLP2: Sub localizes to a region of antiparallel microtubules, in this case the meiotic metaphase central spindle; it is required for central spindle formation; it is required for the localization of other central spindle proteins, and it has nonmotor domain sequence similarity including amino acids that could be phosphorylated by Polo kinase. Similarly, a phylogenetic tree made from the alignment of kinesin motor domain sequences has Sub in a cluster close to the MKLP1 group (Dagenbach, 2004). It is suggested that these features allow Sub to contribute to the organizing of Drosophila acentrosomal spindles by establishing or maintaining the central spindle at prometaphase and metaphase (Jang, 2005).

Mammalian MKLP1 (Matuliene, 2002), Drosophila Pav, and the C. elegans ortholog ZEN-4 have been found in the spindle midzone during anaphase and have an important function in cytokinesis. The midzone has been implicated in establishing the placement of the cytoplasmic furrow, although there are exceptions. Furthermore, MKLP1 was found to bundle microtubules and to promote anti-parallel sliding in vitro (Nislow, 1992). This is consistent with its localization in the spindle midzone, where microtubules overlap in antiparallel orientation. In addition, from the direction of the antiparallel sliding of microtubules it was concluded that MKLP1 is a plus-end-directed motor. Although less is known about MKLP2, it is also required for the spindle midzone and cytokinesis, and like other MKLP1 family members, the protein accumulates at the midzone (Hill, 2000; Fontijn, 2001; Neef, 2003). Characterization of Sub suggests that organisms with two MKLP1-like proteins are not restricted to vertebrates (Jang, 2005).

Two observations suggest that the meiotic metaphase central spindle (MMCS) is mostly or entirely absent in sub mutants: (1) sub mutant spindles lack the prominent band of antiparallel microtubules arising from the overlap of pole to pole spindle fibers; (2) proteins that normally associate with this region, such as Incenp, AurB, and RacGap50C, are absent in sub mutant oocytes. Nonetheless, it is difficult to rule out if other proteins are able to promote formation of a thin and fragile central spindle in sub mutants. A candidate with this function could be Pav but, because of its lethal phenotype and because pav mutant germlines do not make oocytes, it was not possible to determine if Pav contributes to the meiotic spindle assembly. However, the severe defect in meiotic central spindle formation in sub mutants suggests that Pav cannot compensate in a significant way for the absence of Sub (Jang, 2005).

These studies suggest a new role for the central spindle in bipolar spindle formation and chromosome segregation. The localization pattern of central spindle components, such as members of the passenger protein complex AurB and Incenp, is consistent with the idea that a central spindle is forming precociously in oocytes. Although it is typical in Drosophila and human mitotic cells for AurB and Incenp to initially associate with centromeres and then move to the midzone at anaphase, in Drosophila oocytes, these proteins appear on the central spindle much earlier in prometaphase. Furthermore, the meiotic division of Drosophila oocytes appears to skip the stage in mitotic cells (metaphase) where passenger proteins associate with centromeres. No Sub, AurB, or Incenp has been observed at the centromeres during female meiosis; they appear to be associated only with the nonkinetochore microtubules. This appears to be specific only to a subset of midzone proteins. Polo exhibits kinetochore staining typical of mitotic metaphase at meiotic metaphase I. In addition, KLP3A, a kinesinlike protein that associates with the anaphase midzone in mitotic cells, has been reported to stain along the length of female meiotic spindles and only moves to the midzone at anaphase (Jang, 2005).

AurB and Incenp localization to the oocyte MMCS depends on Sub. Similarly, Incenp and AurB midzone localization depends on MKLP2 in mammalian mitotic cells, and MKLP2 may even have a direct interaction with AurB (Gruneberg, 2004). An important aspect of Sub function could be to recruit proteins like AurB in order to stimulate chromosome-microtubule interactions. Consistent with this model, phosphorylation of the microtubule-destabilizing kinesin MCAK by AurB stimulates chromatin induced spindle assembly in Xenopus extracts. It has not been possible, however, to determine the role, if any, of the passenger proteins in meiotic spindle formation (Jang, 2005).

Previous models for acentrosomal spindle formation suggested that the process is initiated by the capture of free microtubules by the chromosomes, followed by bundling and sorting of microtubules by minus-end-directed motors to form the poles. However, these models lack a mechanism to ensure that the kinetochore microtubules are oriented toward only one of two poles. For example, how are the two half spindles oriented relative to each other and what limits the spindle to have only two poles? On the basis of the localization pattern of Sub and the phenotype of sub mutants, a model for acentrosomal spindle formation in Drosophila oocytes is presented that addresses these questions. It is proposed that a structure composed of antiparallel microtubules is organized during prometaphase. The axis of the spindle is defined by this structure, the MMCS, which provides the scaffold on which to build a bipolar spindle during prometaphase and metaphase. Proteins that localize to the spindle poles have a separate function in spindle pole formation and the functions of the central spindle or spindle-poles are partially redundant for maintaining spindle integrity and establishing poles. As the sub; tacc double mutant phenotype demonstrates, in the absence of these structures, the spindle loses all organization (Jang, 2005).

Sub and the MMCS could be required at several points in spindles assembly. The MMCS may have a role in the transition from prometaphase, with its disorganized microtubules around the karyosome, to metaphase with a bipolar spindle. The interaction of kinetochore microtubules with pole-to-pole microtubules of the MMCS via parallel microtubule bundling could determine the formation and relative orientation of only two poles. In addition, Sub probably has a role in maintaining spindle bipolarity. By maintaining the MMCS, Sub could attenuate the activity that is active to establish poles during prometaphase but must be inactive during metaphase. Repeated attempts at new spindle pole formation could generate extra poles in sub mutants. Indeed, what appears to be newly formed short half spindles and the ectopic appearance of TACC in the middle of the spindle of sub mutants were observed, suggesting that de novo pole formation can occur at metaphase. The presence of monopolar spindles could occur if the MMCS has a role in maintaining half spindles, resulting in the collapse of half spindles at metaphase in sub mutants. This dynamic portrayal of the meiotic spindle in sub mutants is consistent with real time observations in ncd mutants. Although wild-type spindles appear to be stable structures over long periods of time, ncd mutant spindles are dynamic structures, where bipolar spindles will form only to lose their organization to become apolar, monopolar, or even completely disassemble and then reform again (Jang, 2005).

The role for the MMCS described above in coordinating spindle pole formation can explain the sub genetic and cytological mutant phenotypes. However, other roles for Sub in chromosome segregation have not been ruled out. An alternative is that Sub contributes to a balance of forces between pushing apart or pulling together the spindle poles. In sub mutants, this could lead to a defect in spindle pole positioning. Two observations argue against this hypothesis. (1) The sub mutant phenotype is not alleviated by defects in ncd (Giunta, 2002), in contrast to Klp61F, which has this role in mitotic cells. (2) This function does not easily explain why sub mutants often have multiple poles, whereas the length of the half spindles are not dramatically shorter than wild-type. Also, a role for Sub in facilitating interactions between the chromosomes and the microtubules cannot be ruled out. This could have a role in aligning the homolog pairs at metaphase I, similar to what has been proposed for the chromokinesin NOD. Although in nod mutants, the nondisjunction phenotype is not associated with defects in spindle organization (Jang, 2005).

Thus a model is favored in which Sub directly contributes to bipolar spindle formation by organizing and/or stabilizing the MMCS. An important implication of this model is that, to compensate for the absence of centrosomes, the oocyte has modified the regulation of the central spindle so that it appears earlier in order to direct spindle formation. This is a novel function for the central spindle and contrasts with the suggestion for mitotic cells that the midzone accumulation of Incenp and AurB needs to be inhibited until anaphase. An important question currently being investigating is what controls Sub localization. One possibility is that the concentration of a factor that promotes microtubule assembly, such as ran-GTP, is greatest in one region of the karyosome. Given the Sub/MKLP2 conservation of sequence and function, it will be interesting to determine if the central spindle has an important role in organizing the acentrosomal spindles of oocytes in mammals and other animals or in plants. Furthermore, as described here for embryos and will be described elsewhere for other mitotic cells , Sub also has a role in spindle assembly of mitotic cells. This is consistent with the hypothesis that acentrosomal spindle assembly occurs through the modification of functions already present in mitotic cells (Jang, 2005).


cDNA clone length - 2498

Bases in 5' UTR - 133

Exons - 3

Bases in 3' UTR - 478


Amino Acids - 628

Structural Domains

It has been suggested that Sub (Giunta, 2002) and Pavarotti (Pav) are two Drosophila kinesinlike proteins in the MKLP1 (or Kinesin 6) family (Nislow, 1992). Although this family was originally defined by MKLP1, Pav, and their orthologues (Dagenbach, 2004), sequence and functional studies suggest it could also include paralogs such as MKLP2 (formerly RabK6; Neef, 2003). In addition, Sub (referred to as DmKlp54E) has been placed on a branch close to the MKLP1 group in a phylogenetic tree derived from the alignment of kinesin motor domain sequences (Dagenbach and Endow, 2004), and there are several conserved amino acids in the neck-linker region of all four proteins that are not present in other kinesins. Pav and MKLP1 have the highest level of amino acid identity or similarity and are probably orthologues. Similarly, there are several identical or similar amino acids in the neck-linker regions of Sub and MKLP2 that are not found in other kinesins. This includes the serine residue in MKLP2 that is phosphorylated by Polo kinase (Neef, 2003) and the corresponding acidic residue at -2 that is often found at Polo kinase sites. Furthermore, although all four of these MKLP1 homologues have nonconserved N-terminal domains of ~100 amino acids, this domain is basic in Pav and MKLP1 but acidic in Sub and MKLP2. These sequence comparisons and the functional studies raise the possibility that Sub is the Drosophila ortholog of MKLP2 (Jang, 2005).


Identification and characterization of MKlp2

Rab guanosine triphosphatases regulate vesicular transport and membrane traffic within eukaryotic cells. A kinesin-like protein that interacts with guanosine triphosphate (GTP)-bound forms of Rab6 has been identified. This protein, termed Rabkinesin-6, was localized to the Golgi apparatus and plays a role in the dynamics of this organelle. The carboxyl-terminal domain of Rabkinesin-6, which contains the Rab6-interacting domain, inhibits the effects of Rab6-GTP on intracellular transport. Thus, a molecular motor is a potential effector of a Rab protein, and coordinated action between members of these two families of proteins could control membrane dynamics and directional vesicular traffic (Echard, 1998).

The Rab6-binding kinesin, Rab6-KIFL, was identified in a two-hybrid screen for proteins that interact with Rab6, a small GTPase involved in membrane traffic through the Golgi apparatus. Rab6-KIFL accumulates in mitotic cells where it localizes to the midzone of the spindle during anaphase, and to the cleavage furrow and midbody during telophase. Overexpression of Rab6-KIFL causes a cell division defect resulting in cell death. Microinjection of antibodies to Rab6-KIFL results in the cells becoming binucleate after one cell cycle, and time-lapse microscopy reveals that this is due to a defect in cleavage furrow formation and thus cytokinesis. These data show that endogenous Rab6-KIFL functions in cell division during cleavage furrow formation and cytokinesis, in addition to its previously described role in membrane traffic (Hill 2000).

The function of mitotic kinesin-like protein (MKlp) 2, a kinesin localized to the central spindle, has been investigated; its depletion results in a failure of cleavage furrow ingression and cytokinesis, and disrupts localization of polo-like kinase 1 (Plk1). MKlp2 is a target for Plk1, and phosphorylated MKlp2 binds to the polo box domain of Plk1. Plk1 also binds directly to microtubules and targets to the central spindle via its polo box domain, and this interaction controls the activity of Plk1 toward MKlp2. An antibody to the neck region of MKlp2 that prevents phosphorylation of MKlp2 by Plk1 causes a cytokinesis defect when introduced into cells. It is proposed that phosphorylation of MKlp2 by Plk1 is necessary for the spatial restriction of Plk1 to the central spindle during anaphase and telophase, and the complex of these two proteins is required for cytokinesis (Neef, 2003).

Mitotic kinases of the Polo and Aurora families are key regulators of chromosome segregation and cytokinesis. This study Investigates the role of MKlp1 and MKlp2, two vertebrate mitotic kinesins essential for cytokinesis, in the spatial regulation of the Aurora B kinase. MKlp2 recruits Polo-like kinase 1 (Plk1) to the central spindle in anaphase. In MKlp2 but not MKlp1-depleted cells, the Aurora B-INCENP complex remains at the centromeres and fails to relocate to the central spindle. MKlp2 exerts dual control over Aurora B localization, because it is a binding partner for Aurora B, and furthermore for the phosphatase Cdc14A. Cdc14A can dephosphorylate INCENP and may contribute to its relocation to the central spindle in anaphase. It is proposed that MKlp2 is involved in the localization of Plk1, Aurora B, and Cdc14A to the central spindle during anaphase, and that the integration of signaling by these proteins is necessary for proper cytokinesis (Gruneberg, 2004).

Cell division is regulated by protein kinases of the Cdk, Polo, and Aurora families. Although it has long been established that temporal control is central to the coordinated action of these kinases, the importance of spatial regulation has only recently been appreciated and is still poorly understood. The kinesin-6 family motor protein MKlp1 is a key regulator of cytokinesis and an ideal substrate for studying spatially regulated protein-phosphorylation events. MKlp1 is negatively regulated by Cdk1 phosphorylation during metaphase and becomes activated in anaphase when cleavage-furrow assembly commences. Aurora B phosphorylates MKlp1 during anaphase and is required for its function in cytokinesis. Another kinesin-6 family motor, MKlp2, mediates the relocation of Aurora B from the centromeres to the central spindle at the onset of anaphase. This study demonstrates that this process is required for the phosphorylation of MKlp1 at S911, an Aurora B consensus site overlapping a bipartite nuclear localization sequence (NLS). MKlp1(S911A) targets to the central spindle but is prematurely imported into the nucleus and fails to support cytokinesis. Spatial restriction of Aurora B to the central spindle by MKlp2 therefore regulates MKlp1 during cytokinesis in human cells (Neef, 2006).

Cdk1 coordinates timely activation of MKlp2 kinesin with relocation of the chromosome passenger complex for cytokinesis

The chromosome passenger complex (CPC) must relocate from anaphase chromosomes to the cell equator for successful cytokinesis during mitosis. Although this landmark event requires the mitotic kinesin MKlp2 (Drosophila homolog: Subito), the spatiotemporal mechanistic basis remains elusive. This study shows that phosphoregulation of MKlp2 by the mitotic kinase Cdk1/cyclin B1 coordinates proper mitotic transition with CPC relocation. Multiple Cdk1/cyclin B1 phosphorylation sites were identified within the stalk and C-terminal tail that inhibit microtubule binding and bundling, oligomerization/clustering, and chromosome targeting of MKlp2. Specifically, inhibition of these abilities by Cdk1/cyclin B1 phosphorylation is essential for proper early mitotic progression. Upon anaphase onset, however, reversal of Cdk1/cyclin B1 phosphorylation promotes MKlp2-CPC complex formation and relocates the CPC from anaphase chromosomes for successful cytokinesis. Thus, it is proposed that phosphoregulation of MKlp2 by Cdk1/cyclin B1 ensures that activation of MKlp2 kinesin and relocation of the CPC occur at the appropriate time and space for proper mitotic progression and genomic stability (Kitagawa, 2014).

subito: Biological Overview | Developmental Biology | Effects of Mutation | References

date revised: 10 December 2005

Home page: The Interactive Fly © 1995, 1996 Thomas B. Brody, Ph.D.

The Interactive Fly resides on the
Society for Developmental Biology's Web server.