Id1 overexpression induces tetraploidization and multiple abnormal mitotic phenotypes by modulating aurora A.
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.
Man
Cornelia
C
Department of Anatomy, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Rosa
Jack
J
Yip
Y L
YL
Cheung
Annie Lai-Man
AL
Kwong
Y L
YL
Doxsey
Stephen J
SJ
Tsao
S W
SW
D020816:Amino Acid Motifs; D064173:Anaphase-Promoting Complex-Cyclosome; D064127:Aurora Kinases; D002460:Cell Line; D016764:Cell Polarity; D002502:Centrioles / Q000201:enzymology; D048749:Cytokinesis; D015536:Down-Regulation; D004795:Enzyme Stability; D005784:Gene Amplification; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D007399:Interphase; D008870:Microtubules / Q000201:enzymology; D008938:Mitosis; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000201:enzymology / Q000473:pathology; D010641:Phenotype; D011123:Polyploidy; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000201:enzymology; D013379:Substrate Specificity; D015533:Transcriptional Activation; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism; D015854:Up-Regulation
C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases