title: AIBp regulates mitotic entry and mitotic spindle assembly by controlling activation of both Aurora-A and Plk1.
abstract: We previously reported that Aurora-A and the hNinein binding protein AIBp facilitate centrosomal structure maintenance and contribute to spindle formation. Here, we report that AIBp also interacts with Plk1, raising the possibility of functional similarity to Bora, which subsequently promotes Aurora-A-mediated Plk1 activation at Thr210 as well as Aurora-A activation at Thr288. In kinase assays, AIBp acts not only as a substrate but also as a positive regulator of both Aurora-A and Plk1. However, AIBp functions as a negative regulator to block phosphorylation of hNinein mediated by Aurora-A and Plk1. These findings suggest a novel AIBp-dependent regulatory machinery that controls mitotic entry. Additionally, knockdown of hNinein caused failure of AIBp to target the centrosome, whereas depletion of AIBp did not affect the localization of hNinein and microtubule nucleation. Notably, knockdown of AIBp in HeLa cells impaired both Aurora-A and Plk1 kinase, resulting in phenotypes with multiple spindle pole formation and chromosome misalignment. Our data show that depletion of AIBp results in the mis-localization of TACC3 and ch-TOG, but not CEP192 and CEP215, suggesting that loss of AIBp dominantly affects the Aurora-A substrate to cause mitotic aberrations. Collectively, our data demonstrate that AIBp contributes to mitotic entry and bipolar spindle assembly and may partially control localization, phosphorylation, and activation of both Aurora-A and Plk1 via hNinein during mitotic progression.
authors.affiliation: a Department of Biochemistry ; Faculty of Medicine; College of Medicine; Kaohsiung Medical University ; Kaohsiung , Taiwan.
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Chou
authors.forename: Joon-Khim
authors.initials: JK
authors.lastname: Loh
authors.forename: Ming-Chang
authors.initials: MC
authors.lastname: Yang
authors.forename: Ching-Chih
authors.initials: CC
authors.lastname: Lin
authors.forename: Ming-Chang
authors.initials: MC
authors.lastname: Hong
authors.forename: Chung-Lung
authors.initials: CL
authors.lastname: Cho
authors.forename: An-Kuo
authors.initials: AK
authors.lastname: Chou
authors.forename: Chi-Huei
authors.initials: CH
authors.lastname: Wang
authors.forename: Ann-Shung
authors.initials: AS
authors.lastname: Lieu
authors.forename: Shen-Long
authors.initials: SL
authors.lastname: Howng
authors.forename: Ching-Mei
authors.initials: CM
authors.lastname: Hsu
authors.forename: Yi-Ren
authors.initials: YR
authors.lastname: Hong
mesh_terms: D064096:Aurora Kinase A / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
chemical_list: D064096:Aurora Kinase A; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C553277:AUNIP protein, human
keywords: AIBp; aurora-A; centrosome; hNinein; mitotic entry; plk1; spindle assembly