title: TRAIP is a regulator of the spindle assembly checkpoint.
abstract: Accurate chromosome segregation during mitosis is temporally and spatially coordinated by fidelity-monitoring checkpoint systems. Deficiencies in these checkpoint systems can lead to chromosome segregation errors and aneuploidy, and promote tumorigenesis. Here, we report that the TRAF-interacting protein (TRAIP), a ubiquitously expressed nucleolar E3 ubiquitin ligase important for cellular proliferation, is localized close to mitotic chromosomes. Its knockdown in HeLa cells by RNA interference (RNAi) decreased the time of early mitosis progression from nuclear envelope breakdown (NEB) to anaphase onset and increased the percentages of chromosome alignment defects in metaphase and lagging chromosomes in anaphase compared with those of control cells. The decrease in progression time was corrected by the expression of wild-type but not a ubiquitin-ligase-deficient form of TRAIP. TRAIP-depleted cells bypassed taxol-induced mitotic arrest and displayed significantly reduced kinetochore levels of MAD2 (also known as MAD2L1) but not of other spindle checkpoint proteins in the presence of nocodazole. These results imply that TRAIP regulates the spindle assembly checkpoint, MAD2 abundance at kinetochores and the accurate cellular distribution of chromosomes. The TRAIP ubiquitin ligase activity is functionally required for the spindle assembly checkpoint control.
authors.affiliation: Service of Dermatology, Lausanne University Hospital, CHUV, 1011 Lausanne, Switzerland.
authors.forename: Christophe
authors.initials: C
authors.lastname: Chapard
authors.affiliation: Department of Cell Physiology and Metabolism, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Meraldi
authors.affiliation: Service of Dermatology, Lausanne University Hospital, CHUV, 1011 Lausanne, Switzerland.
authors.forename: Tobias
authors.initials: T
authors.lastname: Gleich
authors.affiliation: Service of Dermatology, Lausanne University Hospital, CHUV, 1011 Lausanne, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bachmann
authors.affiliation: Service of Dermatology, Lausanne University Hospital, CHUV, 1011 Lausanne, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hohl
authors.affiliation: Service of Dermatology, Lausanne University Hospital, CHUV, 1011 Lausanne, Switzerland marcel.huber@chuv.ch.
authors.forename: Marcel
authors.initials: M
authors.lastname: Huber
mesh_terms: D000705:Anaphase; D002877:Chromosomes, Human / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D059566:M Phase Cell Cycle Checkpoints; D064246:Mad2 Proteins / Q000378:metabolism; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000378:metabolism*
chemical_list: C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
keywords: Chromosome mis-segregation; Mitosis; Spindle assembly checkpoint; TRAF-interacting protein; TRAIP