The Mammalian Passenger Protein TD-60 Is an RCC1 Family Member with an Essential Role in Prometaphase to Metaphase Progression

• Published in: Developmental cell Vol. 5; no. 2; pp. 295 - 307
• Main 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
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-08-2003; Elsevier
• Subjects: Amino Acid Sequence; Biochemistry, Molecular Biology; Calcium-Binding Proteins - metabolism; Cell Cycle Proteins; Cell Division; Chromosomal Proteins, Non-Histone - chemistry; Chromosomal Proteins, Non-Histone - genetics; Chromosomal Proteins, Non-Histone - metabolism; Chromosomes - metabolism; Cloning, Molecular; Guanine Nucleotide Exchange Factors - chemistry; Guanine Nucleotide Exchange Factors - genetics; Guanine Nucleotide Exchange Factors - metabolism; Humans; Life Sciences; Mad2 Proteins; Metaphase; Models, Molecular; Molecular Sequence Data; Nuclear Proteins - chemistry; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; rac1 GTP-Binding Protein - metabolism; Repressor Proteins; RNA, Small Interfering; Sequence Alignment; Spindle Apparatus - metabolism; Tumor Cells, Cultured
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/S1534-5807(03)00205-3

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.