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© The Rockefeller University Press,
0021-9525/2003/9/958-a $5.00
The Journal of Cell Biology, Volume 162, Number 6, 958-a-959
In This Issue |
When nuclear proteins go mitotic
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The first of the mystery proteins is the nucleoporin Nup358, a component of the filaments on the cytoplasmic face of the nuclear envelope. On page 991, Salina et al. show that loss of Nup358 does not block nuclear import but does impair mitosis. During division, cells lacking Nup358 formed abnormal spindles and stalled in metaphase.
Several nuclear pore complex proteins associate with kinetochores in dividing cells, including Nup358. Indeed, the division problems stemmed from abnormal kinetochores. Without Nup358, kinetochore morphology was perturbed, and kinetochore proteins such as dynein, CENP-E, and Mad2 were mislocalized. That the mitotic checkpoint was activated in these cells bolsters the recent argument that checkpoint proteins can signal from the cytoplasm.
The authors postulate that loss of Nup358, a RanGAP-binding protein, could increase local RanGTP levels at chromosomes. Ran is essential for microtubule capture by kinetochores. Thus, the kinetochore errors may be indirect effects of changes in the levels of Ran.
A second nuclear protein with a mitotic function is identified on page 1017 by Raemaekers et al. This novel protein, NuSAP, is found in the nucleoli in interphase cells but is needed for spindle formation and chromosome segregation. The spindle defects in cells lacking NuSAP may stem from a loss of stable microtubule bundles at the central spindle, where the protein sat during mitosis.
Storing mitotic proteins in the nucleus might be a simple way for the cell to separate interphase from mitosis. Through nuclear envelope breakdown, proteins crucial for spindle and kinetochore formation are released, thus committing the cell to division. Conversely, nuclear sequestration could prevent untimely interphase activities, such as the bundling of cytoplasmic microtubules that occurs when NuSAP is overexpressed.
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J. Cell Biol. 2003 162: 1017-1029.
J. Cell Biol. 2003 162: 991-1001.
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