Cloning by differential screening of a Xenopus cDNA that encodes a kinesin-related protein.

Guellec, René Le; Paris, J; Couturier, Antoine; Roghi, C

doi:10.1128/mcb.11.6.3395

Cited by 134 publications

(80 citation statements)

References 26 publications

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“…Agreements to the consensus, within the acceptable substitution range, are indicated by upper case letters. Kiplp from S. cerevisiae (Roof et at., 1992); bimC from A. nidulans (Enos and Morris, 1990); cut7 from S. pombe (Hagan and Yanagida, 1990); Eg5 from Xenopus laevis (Le Guellec et al, 1991); kinesin heavy chain from Drosophila melanogaster (Yang et al, 1989). members of the kinesin-related superfamily, the motor domains of bimC, cut7, Cin8p, Kiplp, and Eg5 from Xenopus laevis (Le Guellec et al, 1991) are most closely related in primary sequence (Fig.…”

Section: Discussionmentioning

confidence: 99%

Two Saccharomyces cerevisiae kinesin-related gene products required for mitotic spindle assembly.

Hoyt

Loo

et al. 1992

The Journal of Cell Biology

390

396

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Abstract. Two Saccharomyces cerevisiae genes, CIN8and KIP1 (a.k.a. CIN9), were identified by their requirement for normal chromosome segregation. Both genes encode polypeptides related to the heavy chain of the microtubule-based force-generating enzyme kinesin. Cin8p was found to be required for pole separation during mitotic spindle assembly at 37~ although overproduced Kiplp could substitute. At lower temperatures, the activity of at least one of these proteins was required for cell viability, indicating that they perform an essential but redundant function. Cin8p was observed to be a component of the mitotic spindle, colocalizing with the microtubules that lie between the poles. Taken together, these findings suggest that these proteins interact with spindle microtubules to produce an outwardly directed force acting upon the poles.

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Section: Discussionmentioning

confidence: 99%

Two Saccharomyces cerevisiae kinesin-related gene products required for mitotic spindle assembly.

Hoyt

Loo

et al. 1992

The Journal of Cell Biology

390

396

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“…Members of the kinesin-5 family are conserved in the amino acid sequence of the motor (forceproducing) domain and apparently perform similar roles in many different cell types (1)(2)(3)(4)(5)(6)(7). Kinesin-5 motors are required for bipolar spindle assembly, and elimination of their function blocks this essential early mitotic step in fungal, insect, and mammalian cells (8 -11).…”

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confidence: 99%

Homotetrameric Form of Cin8p, a Saccharomyces cerevisiae Kinesin-5 Motor, Is Essential for Its in Vivo Function

Hildebrandt

Gheber

Kingsbury

et al. 2006

Journal of Biological Chemistry

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Kinesin-5 motor proteins are evolutionarily conserved and perform essential roles in mitotic spindle assembly and spindle elongation during anaphase. Previous studies demonstrated a specialized homotetrameric structure with two pairs of catalytic domains, one at each end of a dumbbell-shaped molecule. This suggests that they perform their spindle roles by cross-linking and sliding antiparallel spindle microtubules. However, the exact kinesin-5 sequence elements that are important for formation of the tetrameric complexes have not yet been identified. In addition, it has not been demonstrated that the homotetrameric form of these proteins is essential for their biological functions. Thus, we investigated a series of Saccharomyces cerevisiae Cin8p truncations and internal deletions, in order to identify structural elements in the Cin8p sequence that are required for Cin8p functionality, spindle localization, and multimerization. We found that all variants of Cin8p that are functional in vivo form tetrameric complexes. The first coiled-coil domain in the stalk of Cin8p, a feature that is shared by all kinesin-5 homologues, is required for its dimerization, and sequences in the last part of the stalk, specifically those likely involved in coiled-coil formation, are required for Cin8p tetramerization. We also found that dimeric forms of Cin8p that are nonfunctional in vivo can nonetheless bind to microtubules. These findings suggest that binding of microtubules is not sufficient for the functionality of Cin8p and that microtubule cross-linking by the tetrameric complex is essential for Cin8p mitotic functions.Mitotic chromosome segregation is the mechanism by which duplicated genomic information is transmitted to daughter cells during cell division. This essential process is mediated by the mitotic spindle, a highly dynamic, microtubule-based structure that undergoes a distinct set of morphological changes. Many of these changes are achieved by the action of molecular motors from the kinesin-5 (BimC) family, which use ATP hydrolysis to unidirectionally move along microtubules. Members of the kinesin-5 family are conserved in the amino acid sequence of the motor (forceproducing) domain and apparently perform similar roles in many different cell types (1-7). Kinesin-5 motors are required for bipolar spindle assembly, and elimination of their function blocks this essential early mitotic step in fungal, insect, and mammalian cells (8 -11). The yeast Saccharomyces cerevisiae expresses two kinesin-5 motors that overlap in function, Cin8p and Kip1p. Although neither is individually essential, one of the pair is required for viability (2, 3, 12). Loss of KIP1 function causes less severe phenotypes than loss of CIN8, suggesting that Cin8p is more important for successful yeast spindle function (2). Aside from their essential role in spindle assembly, Cin8p and Kip1p are also required for the maintenance of spindle bipolarity following assembly and are responsible for producing most of the spindle-elongating force during anaph...

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“…In nonproliferating cells and tissues in adults, the expression of KSP remains undetectable, whereas its expression is prominent in proliferating cells and tissues during development. 20,55 Increased expression of Eg5 reportedly is associated with tumorigenesis. For example, Castillo et al 20 demonstrated that transgenic mice that overexpressed Eg5 were prone to the development of a variety of tumors.…”

Section: Kinesin-5 Familymentioning

confidence: 99%

The role of kinesin family proteins in tumorigenesis and progression

Feng

2010

Cancer

113

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The kinesin superfamily contains a conserved class of microtubule-dependent molecular motor proteins that possess an adenosine triphosphatase activity and motion characteristics. The active movement of kinesins supports several cellular functions, including mitosis, meiosis, and the transport of macromolecules. Mitosis is a process of eukaryotic cell division that involves the division of nuclei, cytoplasm, organelles, and the cell membrane into 2 daughter cells with roughly equivalent portions of these cellular components. Any errors in this process could result in cell death, abnormality (such as gene deletion, chromosome translocation, or duplication), and cancer. Because mitosis is complex and highly regulated, alteration of kinesin expression or function could lead to carcinogenesis. Moreover, because human cancer is a gene-related disease involving abnormal cell growth, targeting kinesins may create a novel strategy for the control of human cancer. Indeed, several such drugs are being tested successfully in the clinic. In this review, the authors discuss in detail the structure and function of kinesins, the correlation of kinesin expression with tumorigenesis and progression, and the development of biomarkers and cancer-targeted therapy involving the kinesin family proteins. Cancer 2010;116:5150-60.

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Cloning by differential screening of a Xenopus cDNA that encodes a kinesin-related protein.

Cited by 134 publications

References 26 publications

Two Saccharomyces cerevisiae kinesin-related gene products required for mitotic spindle assembly.

Two Saccharomyces cerevisiae kinesin-related gene products required for mitotic spindle assembly.

Homotetrameric Form of Cin8p, a Saccharomyces cerevisiae Kinesin-5 Motor, Is Essential for Its in Vivo Function

The role of kinesin family proteins in tumorigenesis and progression

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