Antizyme1 mediates AURKAIP1-dependent degradation of Aurora-A.

Antizyme1 mediates AURKAIP1-dependent degradation of Aurora-A. Research Abstract Details 

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Antizyme1 mediates AURKAIP1-dependent degradation of Aurora-A. Abstract Text:

S K Lim,G Gopalan,S K Lim,G Gopalan,S K Lim,G Gopalan,

Overexpression of Aurora-A oncogene has been shown to induce genomic instability and tumorigenesis. Cellular levels of Aurora-A are regulated by multiple mechanisms including the proteasome-dependent degradation of Aurora-A protein. Cell-cycle-dependent turnover of Aurora-A protein is mediated by cdh1 through ubiquitin (Ub)- and proteasome-dependent pathway. However, Aurora-A kinase interacting protein 1 (AURKAIP1), a negative regulator of Aurora-A, also promotes proteasome-dependent Aurora-A degradation through an Ub-independent mechanism. In an attempt to understand how AURKAIP1 promotes Aurora-A degradation through Ub-independent pathway, we demonstrate here that antizyme1 (Az1), a well-studied mediator of Ub-independent protein degradation pathway, regulates Aurora-A protein stability. We show that ectopic or polyamine-induced expression of Az1 can lower the steady-state levels of Aurora-A. The effect of Az1 on Aurora-A turnover was shown to be proteasome-dependent, but Ub-independent. Az1 interacts with Aurora-A in vivo and the interaction between Aurora-A and Az1 is essential for the Az1-mediated Aurora-A degradation. Furthermore, we observed that AURKAIP1 could not promote degradation of Aurora-A mutant, which is defective in Az1 interaction. Coexpression of the Az inhibitor (AzI), which downregulates Az1 functions, also abrogated AURKAIP1-mediated degradation of Aurora-A. We further demonstrated that AURKAIP1, Az1 and Aurora-A could exist as a ternary complex and AURKAIP1 enhances the interaction between Az1 and Aurora-A. We propose that AURKAIP1 might function upstream of the Az1 by enhancing the binding affinity of Az1 to Aurora-A to promote recognition, targeting to proteasome and subsequent degradation.

Antizyme1 mediates AURKAIP1-dependent degradation of Aurora-A. Publishing Authors By Initials

SK Lim,G Gopalan,SK Lim,G Gopalan,SK Lim,G Gopalan,

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Antizyme1 mediates AURKAIP1-dependent degradation of Aurora-A. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Oncogene

VOLUME: 26

Page Numbers: 6593-603

Journal Abbreviation: Oncogene

ISSN: 0950-9232

DAY: 23

MONTH: 04

YEAR: 2007

Antizyme1 mediates AURKAIP1-dependent degradation of Aurora-A. Information

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LANGUAGE: eng

NlmUniqueID: 8711562

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AFFILIATION: Laboratory of Gene Structure and Expression, Division of Molecular and Cellular Research, National Cancer Centre, Singapore, Singapore.

Country: England

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MEDLINETA: Oncogene

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