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The mammalian passenger protein TD-60 is an RCC1 family member with an essential role in prometaphase to metaphase progression
Authors:Mollinari Cristiana  Reynaud Caroline  Martineau-Thuillier Stephanie  Monier Solange  Kieffer Sylvie  Garin Jerome  Andreassen Paul R  Boulet Annick  Goud Bruno  Kleman Jean-Philippe  Margolis Robert L
Affiliation:Institut de Biologie Structurale J-P Ebel, CEA-CNRS, 41 rue Jules Horowitz, 38027 Cedex 1, Grenoble, France.
Abstract:Passenger proteins migrate from inner centromeres to the spindle midzone during late mitosis, and those described to date are essential both for proper chromosome segregation and for completion of cell cleavage. We have purified and cloned the human passenger protein TD-60, and we here report that it is a member of the RCC1 family and that it binds preferentially the nucleotide-free form of the small G protein Rac1. Using siRNA, we further demonstrate that the absence of TD-60 substantially suppresses overall spindle assembly, blocks cells in prometaphase, and activates the spindle assembly checkpoint. These defects suggest TD-60 may have a role in global spindle assembly or may be specifically required to integrate kinetochores into the mitotic spindle. The latter is consistent with a TD-60 requirement for recruitment of the passenger proteins survivin and Aurora B, and suggests that like other passenger proteins, TD-60 is involved in regulation of cell cleavage.
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