title: Defects in nuclear pore assembly lead to activation of an Aurora B-mediated abscission checkpoint.
abstract: Correct assembly of nuclear pore complexes (NPCs), which directly and indirectly control nuclear environment and architecture, is vital to genomic regulation. We previously found that nucleoporin 153 (Nup 153) is required for timely progression through late mitosis. In this study, we report that disruption of Nup 153 function by either small interfering RNA-mediated depletion or expression of a dominant-interfering Nup 153 fragment results in dramatic mistargeting of the pore basket components Tpr and Nup 50 in midbody-stage cells. We find a concomitant appearance of aberrantly localized active Aurora B and an Aurora B-dependent delay in abscission. Depletion of Nup 50 is also sufficient to increase the number of midbody-stage cells and, likewise, triggers distinctive mislocalization of Aurora B. Together, our results suggest that defects in nuclear pore assembly, and specifically the basket structure, at this time of the cell cycle activate an Aurora B-mediated abscission checkpoint, thereby ensuring that daughter cells are generated only when fully formed NPCs are present.
authors.affiliation: Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Mackay
authors.forename: Masaki
authors.initials: M
authors.lastname: Makise
authors.forename: Katharine S
authors.initials: KS
authors.lastname: Ullman
mesh_terms: D064107:Aurora Kinase B; D064127:Aurora Kinases; D002467:Cell Nucleus / Q000378:metabolism*; D018816:Genes, cdc; D006367:HeLa Cells; D006801:Humans; D022022:Nuclear Pore / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D014162:Transfection
chemical_list: C121702:NUP50 protein, human; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases