DDA3 recruits microtubule depolymerase Kif2a to spindle poles and controls spindle dynamics and mitotic chromosome movement

Jang, Chang-Young; Wong, Jim; Coppinger, Judith A.; Seki, Akiko; Yates, John R.; Fang, Guowei

doi:10.1083/jcb.200711032

Cited by 67 publications

(117 citation statements)

References 32 publications

(63 reference statements)

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“…Although our results showed clear targeting to the 3Ј-UTR of the KIF2A mRNA, transfection with miR-183 resulted in a significant increase in the presence of cells with monopolar spindles only in HeLa cells, but not in HDF or HTM cells. Formation of bipolar spindles has been reported under conditions of partial knockdown of KIF2A in other cell types (9). The difference on the effects of miR-183 on the formation of monopolar spindles observed between HeLa cells and normal HDF and HTM cells are not likely to depend on differences in targeting the 3Ј-UTR of KIF2A because, in all cases, miR-183 induced a similar decrease in expression of both the KIF2A transcript and protein.…”

Section: Discussionmentioning

confidence: 71%

Targeting of Integrin β1 and Kinesin 2α by MicroRNA 183

Luna

Qiu

et al. 2010

Journal of Biological Chemistry

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MicroRNA 183 (miR-183) has been reported to inhibit tumor invasiveness and is believed to be involved in the development and function of ciliated neurosensory organs. We have recently found that expression of miR-183 increased after the induction of cellular senescence by exposure to H 2 O 2 . To gain insight into the biological roles of miR-183 we investigated two potential novel targets: integrin ␤1 (ITGB1) and kinesin 2␣ (KIF2A). miR-183 significantly decreased the expression of ITGB1 and KIF2A measured by Western blot. Targeting of the 3-untranslated region (3-UTR) of ITGB1 and KIF2A by miR-183 was confirmed by luciferase assay. Transfection with miR-183 led to a significant decrease in cell invasion and migration capacities of HeLa cells that could be rescued by expression of ITGB1 lacking the 3-UTR. Although miR-183 had no effects on cell adhesion in HeLa cells, it significantly decreased adhesion to laminin, gelatin, and collagen type I in normal human diploid fibroblasts and human trabecular meshwork cells. These effects were also rescued by expression of ITGB1 lacking the 3-UTR. Targeting MiR-1832 is predominantly expressed in ciliated ectodermal cells and tissues including retina and hair cells in the organ of Corti and has highly conserved orthologs in both deuterostomes and protostomes. MiR-183 has been found to be up-regulated in the retina of a mouse model of retinitis pigmentosa (1) as well as in colorectal cancer (2-4). Despite its up-regulation in colorectal carcinoma cells, it has been proposed that miR-183 may inhibit the invasiveness of certain cancer cells (5). This potential anti-metastatic role of miR-183 is supported by the observations that miR-183 expression is inversely correlated with the metastatic potential of lung cancer cells. Its ectopic expression in highly metastatic cells can inhibit cell migration and invasion. Furthermore, the expression of the VIL2 coding protein Ezrin, which is known to be functionally important in cancer progression, has been demonstrated to be post-transcriptionally regulated by miR-183 (5).Based on the pattern of tissue expression of miR-183 it has been hypothesized that this miRNA may play some role in the development and function of ciliated neurosensory organs. Specifically, it has been proposed that miR-183 could contribute to reinforcing the post-mitotic differentiated state of hair cells (6). However, functional data for this miRNA is currently limited to the work by Wang et al. (5) on lung cancer cells.We have recently found that, although miR-183 is normally expressed only at low levels in human trabecular meshwork (HTM) cells and human diploid fibroblasts (HDF), its expression increased significantly after the induction of cellular senescence by exposure to H 2 O 2 in these two different cell types (7). Because cellular senescence is recognized as an anticancer mechanism (8), this observation has led us to hypothesize that miR-183 could play a role in the phenotypic changes characteristic of senescent cells, and, in particular, those involved ...

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Section: Discussionmentioning

confidence: 71%

Targeting of Integrin β1 and Kinesin 2α by MicroRNA 183

Luna

Qiu

et al. 2010

Journal of Biological Chemistry

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“…It is interesting to note that no bundling activity of DDA3 is observed in mitotic cells. 2 Thus, it is not clear whether the MT-bundling activity of DDA3 is physiologically relevant to mitosis.…”

Section: Resultsmentioning

confidence: 99%

“…[8][9][10][11][12][13] We recently showed that DDA3 is a regulator of the mitotic spindle essential for mitotic progression. 2 Depletion of DDA3 results in a high frequency of unaligned chromosomes, a substantial reduction in tension across sister kinetochores at metaphase, and a decrease in the velocity of chromosome segregation at anaphase. DDA3 associates with the mitotic spindle and controls MT dynamics.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, DDA3 is a novel mitotic regulator essential for the high fidelity of chromosome segregation. 2 To understand the structure/function relationship of DDA3, we analyzed the domain structure of DDA3 and show here that the N-terminal domain of DDA3 has a novel regulatory function that controls the association of DDA3 with the mitotic spindle.…”

Section: Introductionmentioning

confidence: 99%

“…1 A driving force for the congression and segregation of chromosomes is the dynamic turnover of MTs controlled by MT-associated proteins, such as DDA3, 2 and by MT depolymerases, such as Kif2a. [3][4][5][6][7] DDA3 was initially discovered as a cell cycle regulator activated by p53.…”

Section: Introductionmentioning

confidence: 99%

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The N-terminal domain of DDA3 regulates the spindle-association of the microtubule depolymerase Kif2a and controls the mitotic function of DDA3

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2009

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Shaping microtubules into diverse patterns: Molecular connections for setting up both ends

Mimori-Kiyosue¹

2011

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Microtubules serve as rails for intracellular trafficking and their appropriate organization is critical for the generation of cell polarity, which is a foundation of cell differentiation, tissue morphogenesis, ontogenesis and the maintenance of homeostasis. The microtubule array is not just a static railway network; it undergoes repeated collapse and reassembly in diverse patterns during cell morphogenesis. In the last decade much progress has been made toward understanding the molecular mechanisms governing complex microtubule patterning. This review first revisits the basic principle of microtubule dynamics, and then provides an overview of how microtubules are arranged in highly shaped and functional patterns in cells changing their morphology by factors controlling the fate of microtubule ends. V C 2011 Wiley Periodicals, Inc.

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DDA3 recruits microtubule depolymerase Kif2a to spindle poles and controls spindle dynamics and mitotic chromosome movement

Cited by 67 publications

References 32 publications

Targeting of Integrin β1 and Kinesin 2α by MicroRNA 183

Targeting of Integrin β1 and Kinesin 2α by MicroRNA 183

The N-terminal domain of DDA3 regulates the spindle-association of the microtubule depolymerase Kif2a and controls the mitotic function of DDA3

Shaping microtubules into diverse patterns: Molecular connections for setting up both ends

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