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| Content Provider | PubMed Central |
|---|---|
| Author | Cappell, Kathryn M. Larson, Brittany Sciaky, Noah Whitehurst, Angelique W. |
| Copyright Year | 2010 |
| Abstract | Using a pangenomic loss-of-function screening strategy, we have previously identified 76 potent modulators of paclitaxel responsiveness in non-small-cell lung cancer. The top hit isolated from this screen, symplekin, is a well-established component of the mRNA polyadenylation machinery. Here, we performed a high-resolution phenotypic analysis to reveal the mechanistic underpinnings by which symplekin depletion collaborates with paclitaxel. We find that symplekin supports faithful mitosis by contributing to the formation of a bipolar spindle apparatus. Depletion of symplekin attenuates microtubule polymerization activity as well as expression of the critical microtubule polymerization protein CKAP5 (TOGp). Depletion of additional members of the polyadenylation complex induces similar phenotypes, suggesting that polyadenylation machinery is intimately coupled to microtubule function and thus mitotic spindle formation. Importantly, tumor cells depleted of symplekin display reduced fecundity, but the mitotic defects that we observe are not evident in immortalized cells. These results demonstrate a critical connection between the polyadenylation machinery and mitosis and suggest that tumor cells have an enhanced dependency on these components for spindle assembly. |
| Related Links | http://dx.doi.org/10.1128/mcb.00758-10 |
| Ending Page | 5144 |
| Page Count | 10 |
| Starting Page | 5135 |
| File Format | |
| ISSN | 02707306 |
| e-ISSN | 10985549 |
| Journal | Molecular and Cellular Biology |
| Issue Number | 21 |
| Volume Number | 30 |
| Language | English |
| Publisher | American Society for Microbiology (ASM) |
| Publisher Date | 2010-11-01 |
| Access Restriction | Open |
| Rights Holder | American Society for Microbiology (ASM) |
| Subject Keyword | Cell Biology Molecular Biology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Molecular Biology |
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