Centrosomal Proteins CG-NAP and Kendrin Provide Microtubule Nucleation Sites by Anchoring γ-Tubulin Ring Complex

Takahashi, Mikiko; Yamagiwa, Akiko; Nishimura, Taiichi; Mukai, Hideyuki; Ono, Yoshitaka

doi:10.1091/mbc.e02-02-0112

Cited by 212 publications

(234 citation statements)

References 36 publications

Supporting

Mentioning

225

Contrasting

Order By: Relevance

“…The PCM1 antibody was a kind gift from A Merdes and was used as described previously (Dammermann and Merdes, 2002). The CG-NAP and Kendrin antibodies were a kind gift from Y Ono and used as described previously (Takahashi et al, 1999(Takahashi et al, , 2002.…”

Section: Sirna Transfection and Antibodiesmentioning

confidence: 99%

Centrobin regulates the assembly of functional mitotic spindles

et al. 2010

View full text Add to dashboard Cite

The proper function of the spindle is crucial to the high fidelity of chromosome segregation and is indispensable for tumor suppression in humans. Centrobin is a recently identified centrosomal protein that has a role in stabilizing the microtubule structure. Here we functionally characterize the defects in centrosome integrity and spindle assembly in Centrobin-depleted cells. Centrobin-depleted cells show a range of spindle abnormalities including unfocused poles that are not associated with centrosomes, S-shaped spindles and mini spindles. These cells undergo mitotic arrest and subsequently often die by apoptosis, as determined by live cell imaging. Co-depletion of Mad2 relieves the mitotic arrest, indicating that cells arrest due to a failure to silence the spindle checkpoint in metaphase. Consistent with this, Centrobin-depleted metaphase cells stained positive for BubR1 and BubR1 S676. Staining with a panel of centrosome markers showed a loss of centrosome anchoring to the mitotic spindle. Furthermore, these cells show less cold-stable microtubules and a shorter distance between kinetochore pairs. These results show a requirement of Centrobin in maintaining centrosome integrity, which in turn promotes anchoring of mitotic spindle to the centrosomes. Furthermore, this anchoring is required for the stability of microtubulekinetochore attachments and biogenesis of tension-ridden and properly functioning mitotic spindle.

show abstract

Section: Sirna Transfection and Antibodiesmentioning

confidence: 99%

Centrobin regulates the assembly of functional mitotic spindles

et al. 2010

View full text Add to dashboard Cite

show abstract

“…The AKAP9 protein localizes by immunofluorescence as a single perinuclear dot and some surrounding dispersed fluorescence, corresponding to the centrosome and Golgi compartments, respectively, in interphase HeLa and SaOS2 osteosarcoma cells (19,20). Based on the sequence of the chimeric cDNA, the fusion protein is predicted to lack 2 putative RII binding regions and the centrosome localization domain of AKAP9 (20,22,23).…”

Section: Identification Of Braf Rearrangementmentioning

confidence: 99%

Oncogenic AKAP9-BRAF fusion is a novel mechanism of MAPK pathway activation in thyroid cancer

Ciampi¹,

Knauf²,

Kerler³

et al. 2005

J. Clin. Invest.

115

114

View full text Add to dashboard Cite

Genes crucial for cancer development can be mutated via various mechanisms, which may reflect the nature of the mutagen. In thyroid papillary carcinomas, mutations of genes coding for effectors along the MAPK pathway are central for transformation. BRAF point mutation is most common in sporadic tumors. By contrast, radiation-induced tumors are associated with paracentric inversions activating the receptor tyrosine kinases RET and NTRK1. We report here a rearrangement of BRAF via paracentric inversion of chromosome 7q resulting in an in-frame fusion between exons 1-8 of the AKAP9 gene and exons 9-18 of BRAF. The fusion protein contains the protein kinase domain and lacks the autoinhibitory N-terminal portion of BRAF. It has elevated kinase activity and transforms NIH3T3 cells, which provides evidence, for the first time to our knowledge, of in vivo activation of an intracellular effector along the MAPK pathway by recombination. The AKAP9-BRAF fusion was preferentially found in radiation-induced papillary carcinomas developing after a short latency, whereas BRAF point mutations were absent in this group. These data indicate that in thyroid cancer, radiation activates components of the MAPK pathway primarily through chromosomal paracentric inversions, whereas in sporadic forms of the disease, effectors along the same pathway are activated predominantly by point mutations.

show abstract

“…[1][2][3][4] Pericentrin acts as scaffold within the PCM and interacts with a number of partners, in particular γ-tubulin and other members of the γ-tubulin ring complex, providing a structural framework in which the MTOC activities can occur [5][6][7] (reviewed in ref. 8).…”

Section: Introductionmentioning

confidence: 99%