title: Skp2 is required for Aurora B activation in cell mitosis and spindle checkpoint.
abstract: The Aurora B kinase plays a critical role in cell mitosis and spindle checkpoint. Here, we showed that the ubiquitin E3-ligase protein Skp2, also as a cell-cycle regulatory protein, was required for the activation of Aurora B and its downstream protein. When we restored Skp2 knockdown Hela cells with Skp2 and Skp2-LRR E3 ligase dead mutant we found that Skp2 could rescue the defect in the activation of Aurora B, but the mutant failed to do so. Furthermore, we discovered that Skp2 could interact with Aurora B and trigger Aurora B Lysine (K) 63-linked ubiquitination. Finally, we demonstrated the essential role of Skp2 in cell mitosis progression and spindle checkpoint, which was Aurora B dependent. Our results identified a novel ubiquitinated substrate of Skp2, and also indicated that Aurora B ubiquitination might serve as an important event for Aurora B activation in cell mitosis and spindle checkpoint.
authors.affiliation: a Guangzhou Key Laboratory of Translational Medicine on Malignant Tumor Treatment; Affiliated Tumor Hospital of Guangzhou Medical University ; Guangzhou , China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wu
authors.affiliation: a Guangzhou Key Laboratory of Translational Medicine on Malignant Tumor Treatment; Affiliated Tumor Hospital of Guangzhou Medical University ; Guangzhou , China.
authors.forename: Yu-Fan
authors.initials: YF
authors.lastname: Huang
authors.affiliation: b The Fifth Affiliated Hospital of Guangzhou Medical University ; Guangzhou , China.
authors.forename: Xin-Ke
authors.initials: XK
authors.lastname: Zhou
authors.affiliation: c State Key Laboratory of Oncology in South China and Department of Experimental Research; Sun Yat-Sen University Cancer Center ; Guangzhou , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: c State Key Laboratory of Oncology in South China and Department of Experimental Research; Sun Yat-Sen University Cancer Center ; Guangzhou , China.
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Lian
authors.affiliation: d Nanchang Key Laboratory of Cancer Pathogenesis and Translational Research; the Third Affiliated Hospital; Nanchang University ; Nanchang , China.
authors.forename: Xiao-Bin
authors.initials: XB
authors.lastname: Lv
authors.affiliation: a Guangzhou Key Laboratory of Translational Medicine on Malignant Tumor Treatment; Affiliated Tumor Hospital of Guangzhou Medical University ; Guangzhou , China.
authors.forename: Xiu-Rong
authors.initials: XR
authors.lastname: Gao
authors.affiliation: e Department of Molecular and Cellular Oncology ; The University of Texas M. D. Anderson Cancer Center ; Houston , TX USA.
authors.forename: Hui-Kuan
authors.initials: HK
authors.lastname: Lin
authors.affiliation: c State Key Laboratory of Oncology in South China and Department of Experimental Research; Sun Yat-Sen University Cancer Center ; Guangzhou , China.
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.affiliation: a Guangzhou Key Laboratory of Translational Medicine on Malignant Tumor Treatment; Affiliated Tumor Hospital of Guangzhou Medical University ; Guangzhou , China.
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Huang
mesh_terms: D000818:Animals; D064107:Aurora Kinase B / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D005434:Flow Cytometry; D042822:Genomic Instability / Q000235:genetics / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D051379:Mice; D018345:Mice, Knockout; D008938:Mitosis / Q000235:genetics / Q000502:physiology; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D044786:S-Phase Kinase-Associated Proteins; D064107:Aurora Kinase B
keywords: Aurora B; Skp2; cell mitosis; genomic stability; spindle checkpoint; tumorigenesis; ubiquitination