Open AccessThe N-terminal domain of the Aurora-A Phe-31 variant encodes an E3 ubiquitin ligase and mediates ubiquitination of IκBα
Author(s) -
Paraskevi Briassouli,
Florence Chan,
Spiros Linardopoulos
Publication year - 2006
Publication title -
human molecular genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.811
H-Index - 276
eISSN - 1460-2083
pISSN - 0964-6906
DOI - 10.1093/hmg/ddl410
Subject(s) - ubiquitin ligase , biology , ubiquitin , ectopic expression , microbiology and biotechnology , dna ligase , centrosome , genetics , mitosis , gene , cell cycle
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.
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