Control of centrin stability by Aurora A

• Published in: PloS one Vol. 6; no. 6; p. e21291
• Main Authors: Lukasiewicz, Kara B, Greenwood, Tammy M, Negron, Vivian C, Bruzek, Amy K, Salisbury, Jeffrey L, Lingle, Wilma L
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23-06-2011; Public Library of Science (PLoS)
• Subjects: Adenomatous polyposis coli; Amplification; Anaphase-Promoting Complex-Cyclosome; Aurora Kinases; Biochemistry; Biology; Breast cancer; Calcium-Binding Proteins - metabolism; Cancer; Cell cycle; Cell Cycle Proteins - metabolism; Cell Proliferation; Centrosome - metabolism; Centrosomes; Control stability; Deoxyribonucleic acid; DNA; Genetic transformation; HeLa Cells; Humans; Kinases; Laboratories; Medicine; Metaphase; Microscopy; Mitosis; Molecular biology; Mutation; Mutation - genetics; Overexpression; Pathology; Phosphorylation; Prophase; Proteasomes; Protein Binding; Protein Stability; Protein Transport; Protein-Serine-Threonine Kinases - metabolism; Protein-serine/threonine kinase; Proteins; Regulation; Serine - metabolism; Threonine; Transformation; Tumors; Ubiquitin-Protein Ligase Complexes - metabolism; United States > US; Minnesota
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0021291

Aurora A is an oncogenic serine/threonine kinase which can cause cell transformation and centrosome amplification when over-expressed. Human breast tumors show excess Aurora A and phospho-centrin in amplified centrosomes. Here, we show that Aurora A mediates the phosphorylation of and localizes with centrin at the centrosome, with both proteins reaching maximum abundance from prophase through metaphase, followed by their precipitous loss in late stages of mitosis. Over-expression of Aurora A results in excess phospho-centrin and centrosome amplification. In contrast, centrosome amplification is not seen in cells over-expressing Aurora A in the presence of a recombinant centrin mutant lacking the serine phosphorylation site at residue 170. Expression of a kinase dead Aurora A results in a decrease in mitotic index and abrogation of centrin phosphorylation. Finally, a recombinant centrin mutation that mimics centrin phosphorylation increases centrin's stability against APC/C-mediated proteasomal degradation. Taken together, these results suggest that the stability of centrin is regulated in part by Aurora A, and that excess phosphorylated centrin may promote centrosome amplification in cancer.