AI Article Synopsis
- The anaphase promoting complex (APC) plays a key role in protein degradation as cells transition from mitosis to S-phase, with its activity regulated by phosphorylation.
- Various antimitotic drugs (taxol, nocodazole, vincristine, monastrol) were used to arrest HeLa S3 cells in prometaphase, revealing differences in phosphorylation patterns across the APC despite similar arrest states.
- The study highlights that the phosphorylation status of the APC is dynamic during drug-induced mitotic arrest, which may have implications for the effectiveness of antimitotic drugs in cancer treatment.
Article Abstract
The anaphase promoting complex (APC) controls the degradation of proteins during exit from mitosis and entry into S-phase. The activity of the APC is regulated by phosphorylation during mitosis. Because the phosphorylation pattern provides insights into the complexity of regulation of the APC, we studied in detail the phosphorylation patterns at a single mitotic state of arrest generated by various antimitotic drugs. We examined the phosphorylation patterns of the APC in HeLa S3 cells after they were arrested in prometaphase with taxol, nocodazole, vincristine, or monastrol. There were 71 phosphorylation sites on nine of the APC subunits. Despite the common state of arrest, the various antimitotic drug treatments resulted in differences in the phosphorylation patterns and phosphorylation stoichiometries. The relative phosphorylation stoichiometries were determined by using a method adapted from the isotope-free quantitation of the extent of modification (iQEM). We could show that during drug arrest the phosphorylation state of the APC changes, indicating that the mitotic arrest is not a static condition. We discuss these findings in terms of the variable efficacy of antimitotic drugs in cancer chemotherapy.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2329673 | PMC |
| http://dx.doi.org/10.1073/pnas.0709807104 | DOI Listing |
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