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Role of centrosomal adaptor proteins of the TACC family in the regulation of microtubule dynamics during mitotic cell division.

Biological chemistry (2013-06-22)
Harish C Thakur, Madhurendra Singh, Luitgard Nagel-Steger, Daniel Prumbaum, Eyad Kalawy Fansa, Lothar Gremer, Hakima Ezzahoini, André Abts, Lutz Schmitt, Stefan Raunser, Mohammad R Ahmadian, Roland P Piekorz
RESUMEN

During the mitotic division cycle, cells pass through an extensive microtubule rearrangement process where microtubules forming the mitotic spindle apparatus are dynamically instable. Several centrosomal- and microtubule-associated proteins are involved in the regulation of microtubule dynamics and stability during mitosis. Here, we focus on members of the transforming acidic coiled coil (TACC) family of centrosomal adaptor proteins, in particular TACC3, in which their subcellular localization at the mitotic spindle apparatus is controlled by Aurora-A kinase-mediated phosphorylation. At the effector level, several TACC-binding partners have been identified and characterized in greater detail, in particular, the microtubule polymerase XMAP215/ch-TOG/CKAP5 and clathrin heavy chain (CHC). We summarize the recent progress in the molecular understanding of these TACC3 protein complexes, which are crucial for proper mitotic spindle assembly and dynamics to prevent faulty cell division and aneuploidy. In this regard, the (patho)biological role of TACC3 in development and cancer will be discussed.