Transforming Acidic Coiled-coil-containing Protein 4 Interacts with Centrosomal AKAP350 and the Mitotic Spindle Apparatus

Steadman, Brent T.; Schmidt, P. Henry; Shanks, Ryan A.; Lapierre, Lynne A.; Goldenring, James R.

doi:10.1074/jbc.m201914200

Cited by 29 publications

(26 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To date, only a few coiled-coil structures have been found to be involved in centrosome localization and, yet, these structures usually vary in length or share low homology in primary sequences. We have noted that the coiled-coil region of TACC4 is similar to that of Su48 in length and can target the protein to the centrosome by association with a related centrosome anchor protein AKAP350 (28). However, the coiled coil of Su48 shares little homology to the comparable region of TACC4 or other centrosomal proteins.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Su48, a centrosome protein essential for cell division

Wang

Du²,

Meinkoth³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The centrosome functions as the major microtubule-organizing center and plays a vital role in guiding chromosome segregation during mitosis. Centrosome abnormalities are frequently seen in a variety of cancers, suggesting that dysfunction of this organelle may contribute to malignant transformation. In our efforts to identify the protein components of the centrosome and to understand the structure features involved in the assembly and functions of this organelle, we cloned and characterized a centrosome-associated protein called Su48. We found that a coiled coil-containing subdomain of Su48 was both sufficient and required for its centrosome localization. In addition, this structure also modulates Su48 dimerization. Moreover, ectopic expression of Su48 causes abnormal mitosis, and a mutant form of Su48 disrupts the localization of ␥-tubulin to the centrosome. Finally, by microinjection of an anti-Su48 antibody, we found that disruption of normal Su48 functions leads to mitotic failure, possibly due to centrosome defects or incomplete cytokinesis. Thus, Su48 represents a previously unrecognized centrosome protein that is essential for cell division. We speculate that Su48 abnormalities may cause aberrant chromosome segregation and may contribute to aneuploidy and malignant transformation.cancer ͉ coiled coil ͉ mitosis

show abstract

Section: Discussionmentioning

confidence: 99%

Characterization of Su48, a centrosome protein essential for cell division

Wang

Du²,

Meinkoth³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Positive results were recorded if ␤-galactosidase assay was positive within 3 h. All constructs were tested for auto-activation. We used an established AKAP350-interacting protein, TACC3, cloned into pAD vector as a positive control for direct interaction (31). Results are representative of three independent experiments.…”

Section: Yeast Two-hybrid Assaysmentioning

confidence: 99%

“…Mass spectrometry analysis of different AKAP350A-scaffolded protein complexes revealed that two centrosomal proteins, Cdk5RAP2 and Cep170, interact specifically with AKAP350A constructs containing the MTNC-promoting region and therefore likely play roles in regulation of microtubule nucleation. Another centrosomal protein, Cep68, associated with AKAP350A distal to the promoting region in the far C-terminal sequence of AKAP350A, which also contains the PACT domain and the binding region for TACC3 (31).…”

Section: Akap350a Promotes Microtubule Nucleationmentioning

confidence: 99%

See 1 more Smart Citation

The C-terminal region of A-kinase anchor protein 350 (AKAP350A) enables formation of microtubule-nucleation centers and interacts with pericentriolar proteins

Kolobova

Roland

Lapierre

et al. 2017

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Edited by Velia M. Fowler Microtubules in animal cells assemble (nucleate) from both the centrosome and the cis-Golgi cisternae. A-kinase anchor protein 350 kDa (AKAP350A, also called AKAP450/CG-NAP/ AKAP9) is a large scaffolding protein located at both the centrosome and Golgi apparatus. Previous findings have suggested that AKAP350 is important for microtubule dynamics at both locations, but how this scaffolding protein assembles microtubule nucleation machinery is unclear. Here, we found that overexpression of the C-terminal third of AKAP350A, enhanced GFP-AKAP350A(2691-3907), induces the formation of multiple microtubule-nucleation centers (MTNCs). Nevertheless, these induced MTNCs lacked "true" centriole proteins, such as Cep135. Mapping analysis with AKAP350A truncations demonstrated that AKAP350A contains discrete regions responsible for promoting or inhibiting the formation of multiple MTNCs. Moreover, GFP-AKAP350A (2691-3907) recruited several pericentriolar proteins to MTNCs, including ␥-tubulin, pericentrin, Cep68, Cep170, and Cdk5RAP2. Proteomic analysis indicated that Cdk5RAP2 and Cep170 both interact with the microtubule nucleation-promoting region of AKAP350A, whereas Cep68 interacts with the distal C-terminal AKAP350A region. Yeast two-hybrid assays established a direct interaction of Cep170 with AKAP350A. Super-resolution and deconvolution microscopy analyses were performed to define the association of AKAP350A with centrosomes, and these studies disclosed that AKAP350A spans the bridge between centrioles, co-localizing with rootletin and Cep68 in the linker region. siRNA-mediated depletion of AKAP350A caused displacement of both Cep68 and Cep170 from the centrosome. These results suggest that AKAP350A acts as a scaffold for factors involved in microtubule nucleation at the centrosome and coordinates the assembly of protein complexes associating with the intercentriolar bridge.

show abstract

“…Pericentrin and another anchoring protein, AKAP350/450, both target PKA and protein kinase C (PKC) to sites within the centrosome. However, the latter can also anchor the additional binding partners PP1, PP2B, phosphodiesterase (PDE), protein kinase N (PKN), TACC3 and CLIC4 (Diviani et al, 2000;Chen et al, 2004;Steadman et al, 2002). The repertoire of AKAP targeting may also be increased through transcriptional regulation.…”

mentioning

confidence: 99%