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Document Type |
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Article In Journal |
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Document Title |
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Depletion of the Ras Association Domain Family 1, Isoform A–Associated Novel Microtubule-Associated Protein, C19ORF5/MAP1S, Causes Mitotic Abnormalities Depletion of the Ras Association Domain Family 1, Isoform A–Associated Novel Microtubule-Associated Protein, C19ORF5/MAP1S, Causes Mitotic Abnormalities |
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Document Language |
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English |
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Abstract |
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Ras association domain family 1, isoform A (RASSF1A) is a
novel tumor suppressor gene that is found to be inactivated in
more than 40 types of sporadic cancers. In addition, mouse
Rassf1a knockout models have an increased frequency of
spontaneous and induced tumors. The mechanisms by which
RASSF1A exerts its tumor suppression activities or the
pathways it can regulate are not yet fully understood. Using
yeast two-hybrid system, we have previously identified
C19ORF5/MAP1S as the major RASSF1A-interacting protein.
C19ORF5 has two conserved microtubule-associated regions
and may function to anchor RASSF1A to the centrosomes.
In this study, we have analyzed the cellular functions of
C19ORF5. By using small interfering RNA–mediated depletion
and time-lapse video microscopy, we show that C19ORF5
knockdown causes mitotic abnormalities that consist of
failure to form a stable metaphase plate, premature sister
chromatid separation, lagging chromosomes, and multipolar
spindles. We also show that a fraction of C19ORF5 localizes to
the spindle microtubules. Additionally, we show here that
C19ORF5 localizes to the microtubule-organizing centers
during microtubule regrowth after nocodazole washout.
Knockdown of C19ORF5 disrupts the microtubule-organizing
center and results in microtubule nucleation from several
sites. Whereas the localization of pericentrin is not affected,
A- and ;-tubulin localization and sites of nucleation are
greatly altered by C19ORF5 depletion. This may indicate
that C19ORF5 plays a role in anchoring the microtubuleorganizing
center to the centrosomes. In addition, we show
that the NH2 terminus of C19ORF5 is essential for this process.
This novel role for C19ORF5 could explain the resulting
mitotic abnormalities that occur on its depletion and can
potentially provide an underlying mechanism for the frequent
centrosome and microtubule abnormalities detected in
several cancers. |
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ISSN |
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1538-7445 |
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Journal Name |
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Cancer Res. |
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Volume |
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67 |
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Issue Number |
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2 |
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Publishing Year |
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1428 AH
2007 AD |
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Article Type |
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Article |
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Added Date |
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Monday, April 26, 2010 |
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Researchers
| أشرف دلول | Dallol, Ashraf | Investigator | Doctorate | a.dallol@bham.ac.uk |
| فريدة لطيف | latif, Farida | Investigator | Doctorate | f.latif@bham.ac.uk |
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