title: The centrosomal adaptor TACC3 and the microtubule polymerase chTOG interact via defined C-terminal subdomains in an Aurora-A kinase-independent manner.
abstract: The cancer-associated, centrosomal adaptor protein TACC3 (transforming acidic coiled-coil 3) and its direct effector, the microtubule polymerase chTOG (colonic and hepatic tumor overexpressed gene), play a crucial function in centrosome-driven mitotic spindle assembly. It is unclear how TACC3 interacts with chTOG. Here, we show that the C-terminal TACC domain of TACC3 and a C-terminal fragment adjacent to the TOG domains of chTOG mediate the interaction between these two proteins. Interestingly, the TACC domain consists of two functionally distinct subdomains, CC1 (amino acids (aa) 414-530) and CC2 (aa 530-630). Whereas CC1 is responsible for the interaction with chTOG, CC2 performs an intradomain interaction with the central repeat region of TACC3, thereby masking the TACC domain before effector binding. Contrary to previous findings, our data clearly demonstrate that Aurora-A kinase does not regulate TACC3-chTOG complex formation, indicating that Aurora-A solely functions as a recruitment factor for the TACC3-chTOG complex to centrosomes and proximal mitotic spindles. We identified with CC1 and CC2, two functionally diverse modules within the TACC domain of TACC3 that modulate and mediate, respectively, TACC3 interaction with chTOG required for spindle assembly and microtubule dynamics during mitotic cell division.
authors.affiliation: From the Institut für Biochemie und Molekularbiologie II, Medizinische Fakultät der Heinrich-Heine-Universität, D-40225 Düsseldorf, Germany.
authors.forename: Harish C
authors.initials: HC
authors.lastname: Thakur
authors.forename: Madhurendra
authors.initials: M
authors.lastname: Singh
authors.forename: Luitgard
authors.initials: L
authors.lastname: Nagel-Steger
authors.forename: Jana
authors.initials: J
authors.lastname: Kremer
authors.forename: Daniel
authors.initials: D
authors.lastname: Prumbaum
authors.forename: Eyad Kalawy
authors.initials: EK
authors.lastname: Fansa
authors.forename: Hakima
authors.initials: H
authors.lastname: Ezzahoini
authors.forename: Kazem
authors.initials: K
authors.lastname: Nouri
authors.forename: Lothar
authors.initials: L
authors.lastname: Gremer
authors.forename: André
authors.initials: A
authors.lastname: Abts
authors.forename: Lutz
authors.initials: L
authors.lastname: Schmitt
authors.forename: Stefan
authors.initials: S
authors.lastname: Raunser
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Ahmadian
authors.forename: Roland P
authors.initials: RP
authors.lastname: Piekorz
mesh_terms: D000818:Animals; D064096:Aurora Kinase A / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism*; D005326:Fetal Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary
chemical_list: C454180:CKAP5 protein, human; D002352:Carrier Proteins; D005326:Fetal Proteins; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; C120551:TACC3 protein, human; C418485:TACC3 protein, mouse; C576917:AURKA protein, human; C576918:Aurka protein, mouse; D064096:Aurora Kinase A
keywords: Aurora-A; Centrosome; Coiled-Coil; Microtubules; Mitosis; Mitotic Spindle; Protein Domains; Protein Interaction; TACC3; chTOG