AKAP95 interacts with nucleoporin TPR in mitosis and is important for the spindle assembly checkpoint |
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| Authors: | Graciela López-Soop Torunn Rønningen Agnieszka Rogala Nina Richartz Heidi Kiil Blomhoff Bernd Thiede |
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| Institution: | 1. Department of Molecular Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway;2. Norwegian Center for Stem Cell Research, Oslo University Hospital, Oslo, Norway;3. Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway;4. Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway |
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| Abstract: | Faithful chromosome segregation during mitosis relies on a proofreading mechanism that monitors proper kinetochore-microtubule attachments. The spindle assembly checkpoint (SAC) is based on the concerted action of numerous components that maintain a repressive signal inhibiting transition into anaphase until all chromosomes are attached. Here we show that A-Kinase Anchoring Protein 95 (AKAP95) is necessary for proper SAC function. AKAP95-depleted HeLa cells show micronuclei formed from lagging chromosomes at mitosis. Using a BioID proximity-based proteomic screen, we identify the nuclear pore complex protein TPR as a novel AKAP95 binding partner. We show interaction between AKAP95 and TPR in mitosis, and an AKAP95-dependent enrichment of TPR in the spindle microtubule area in metaphase, then later in the spindle midzone area. AKAP95-depleted cells display faster prometaphase to anaphase transition, escape from nocodazole-induced mitotic arrest and show a partial delocalization from kinetochores of the SAC component MAD1. Our results demonstrate an involvement of AKAP95 in proper SAC function likely through its interaction with TPR. |
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| Keywords: | mitotic arrest deficient translocated in promoter region |
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