title: IQGAP1 interacts with Aurora-A and enhances its stability and its role in cancer.
abstract: IQGAP1, a ubiquitously expressed scaffold protein, has been identified in a wide range of organisms. It participates in multiple aspects of cellular events by binding to and regulating numerous interacting proteins. In our present study, we identified a new IQGAP1 binding protein named Aurora-A which is an oncogenic protein and overexpressed in various types of human tumors. In vitro analysis with GST-Aurora-A fusion proteins showed a physical interaction between Aurora-A and IQGAP1. Moreover, the binding also occurred in HeLa cells as endogenous Aurora-A co-immunoprecipitated with IQGAP1 from the cell lysates. Overexpression of IQGAP1 resulted in an elevation of both expression and activity of Aurora-A kinase. Endogenous IQGAP1 knockdown by siRNA promoted Aurora-A degradation whereas IQGAP1 overexpression enhanced the stability of Aurora-A. Additionally, we documented that the IQGAP1-induced cell proliferation was suppressed by knocking down Aurora-A expression. Taken together, our results showed an unidentified relationship between Aurora-A and IQGAP1, and provided a new insight into the molecular mechanism by which IQGAP1 played a regulatory role in cancer.
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Pan Jia Yuan Nan Li, Beijing 100021, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Yin
authors.forename: Ji
authors.initials: J
authors.lastname: Shi
authors.forename: Dapeng
authors.initials: D
authors.lastname: Wang
authors.forename: Tong
authors.initials: T
authors.lastname: Tong
authors.forename: Mingrong
authors.initials: M
authors.lastname: Wang
authors.forename: Feiyue
authors.initials: F
authors.lastname: Fan
authors.forename: Qimin
authors.initials: Q
authors.lastname: Zhan
mesh_terms: D064127:Aurora Kinases; D049109:Cell Proliferation; D004795:Enzyme Stability; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D020703:ras GTPase-Activating Proteins / Q000378:metabolism*
chemical_list: C101203:IQ motif containing GTPase activating protein 1; D020703:ras GTPase-Activating Proteins; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases