The N-terminal domain of the Aurora-A Phe-31 variant encodes an E3 ubiquitin ligase and mediates ubiquitination of IkappaBalpha.
Aurora-A is an important regulator of mitosis and is frequently amplified in human cancer. Ectopic expression of Aurora-A in mammalian cells induces centrosome amplification, genomic instability and transformation. A common genetic variant in Aurora-A (F31I) is preferentially amplified and is associated with the occurrence and the status of colon, oesophageal ... and breast cancers. Here we demonstrate that the N-terminal domain of Aurora-A Phe-31 variant exhibits an intrinsic ubiquitin ligase activity. Mutation of cysteines 8, 33 and 49 of Aurora-A abolishes the ubiquitin ligase activity of the protein. Aurora-A in a complex with UBE2N/MMS2 catalyses polyubiquitination of IkappaBalpha in vitro and in vivo.
Mesh Terms:
Amino Acid Sequence, Conserved Sequence, Humans, I-kappa B Kinase, Molecular Sequence Data, Mutation, Phenylalanine, Protein Binding, Protein-Serine-Threonine Kinases, Sequence Alignment, Ubiquitin, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases
Amino Acid Sequence, Conserved Sequence, Humans, I-kappa B Kinase, Molecular Sequence Data, Mutation, Phenylalanine, Protein Binding, Protein-Serine-Threonine Kinases, Sequence Alignment, Ubiquitin, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases
Hum. Mol. Genet.
Date: Nov. 15, 2006
PubMed ID: 17060341
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