Id1 overexpression induces tetraploidization and multiple abnormal mitotic phenotypes by modulating aurora A
Graduate School of Biomedical Sciences; Program in Molecular Medicine
Medical Subject Headings
Amino Acid Motifs; Cell Line; Cell Polarity; Centrioles; Cytokinesis; Down-Regulation; Enzyme Stability; Gene Amplification; Humans; Inhibitor of Differentiation Protein 1; Interphase; Microtubules; *Mitosis; Mitotic Spindle Apparatus; Mutation; Neoplasms; Phenotype; *Polyploidy; Promoter Regions, Genetic; Protein Binding; Protein Processing, Post-Translational; Protein-Serine-Threonine Kinases; Substrate Specificity; Transcriptional Activation; Ubiquitin-Protein Ligase Complexes; Up-Regulation
Life Sciences | Medicine and Health Sciences
The basic helix-loop-helix transcription factor, Id1, was shown to induce tetraploidy in telomerase-immortalized nasopharyngeal epithelial cells in this study. Using both transient and stable Id1-expressing cell models, multiple mitotic aberrations were detected, including centrosome amplification, binucleation, spindle defects, and microtubule perturbation. Many of these abnormal phenotypes have previously been reported in cells overexpressing Aurora A. Further experiments showed that Id1 could stabilize Aurora A, whereas knocking down Aurora A expression in Id1-expressing cells could rescue some of the mitotic defects. The mechanisms by which Aurora A could be modulated by Id1 were explored. DNA amplification of the Aurora A locus was not involved. Id1 could only weakly activate the transcriptional activity of the Aurora A promoter. We found that Id1 overexpression could affect Aurora A degradation, leading to its stabilization. Aurora A is normally degraded from mitosis exit by the APC/C(Cdh1)-mediated proteasomal proteolysis pathway. Our results revealed that Id1 and Cdh1 are binding partners. The association of Id1 and Cdh1 was found to be dependent on the canonical destruction box motif of Id1, the increased binding of which may compete with the interaction between Cdh1 and Aurora A, leading to stabilization of Aurora A in Id1-overexpressing cells.
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Citation: Mol Biol Cell. 2008 Jun;19(6):2389-401. Epub 2008 Mar 19. Link to article on publisher's site
Molecular biology of the cell
Man, Cornelia; Rosa, Jack; Yip, Y. L.; Cheung, Annie Lai-Man; Kwong, Yok-Lam; Doxsey, Stephen J.; and Tsao, Sai Wah, "Id1 overexpression induces tetraploidization and multiple abnormal mitotic phenotypes by modulating aurora A" (2008). GSBS Student Publications. 1467.