Control At The Cell Center: The Role Of Spindle Poles In Cytoskeletal Organization And Cell Cycle Regulation

Cuschieri, Lara; Nguyen, Thao; Vogel, Jackie

doi:10.4161/cc.6.22.4941

Cited by 28 publications

(28 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several groups have observed mitotic-specific associations of RASS-F1A with g-tubulin within centromeres near the region of the microtubule-organizing center. The microtubuleorganizing center is a region, whereby microtubules emerge and is a site of microtubule nucleation and an abundance of g-tubulin (Moshnikova et al, 2006;Cuschieri et al, 2007;Raynaud-Messina and Merdes, 2007). RASSF1A localizes to spindle poles and centromeric areas during metaphase and anaphase, most likely in association with g-tubulin.…”

Section: Introductionmentioning

confidence: 99%

Functional importance of RASSF1A microtubule localization and polymorphisms

2010

View full text Add to dashboard Cite

Ras association domain family protein 1A (RASSF1A) is one of the more heavily methylated genes in human cancers. In addition to promoter-specific methylation, RASSF1A polymorphisms have been identified in cancer patients. RASSF1A is a tumor suppressor protein involved in death receptor-dependent apoptosis and it is localized to microtubules. Currently, the biological importance of RASSF1A microtubule localization and the functional consequences of RASSF1A polymorphisms is not understood. In this study, we have investigated both RASSF1A microtubule association and polymorphisms. Loss of RASSF1A microtubule association resulted in the nuclear appearance of RASSF1A and the loss of association with a-, c-and b-tubulin. Moreover, the loss of microtubule localization of RASSF1A resulted in enhanced tumorpromoting potential, as determined by a xenograft transplantation model in nude mice. It is surprising that, several RASSF1A polymorphisms also lost the ability to associate with a-, c-and b-tubulin and lost the ability to prevent tumor formation in a xenograft nude mouse model when compared with wild-type RASSF1A. Our results demonstrate a role for RASSF1A microtubule localization in eliciting its tumor suppressor function. In addition, some RASSF1A polymorphisms lack the tumor suppressor function of RASSF1A and, if present in patients, may be tumorigenic.

show abstract

Section: Introductionmentioning

confidence: 99%

Functional importance of RASSF1A microtubule localization and polymorphisms

2010

View full text Add to dashboard Cite

show abstract

“…Recent studies have shown they are also crucial for multiple steps throughout the entire cell cycle (2)(3)(4). Removal of centrosomes by microsurgery or laser ablation leads to G1 arrest of the acentriolar cell (5,6), and G1 arrest was also observed after siRNA-mediated depletion of proteins from the pericentriolar material or the centrioles (7).…”

mentioning

confidence: 99%

Discovery of a distinct domain in cyclin A sufficient for centrosomal localization independently of Cdk binding

Pascreau

Eckerdt

Churchill

et al. 2010

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

View full text Add to dashboard Cite

Centrosomes have recently emerged as key regulators of the cell cycle. The G1/S transition requires a functional centrosome, and centrosomal localization of numerous proteins, including cyclin/Cdk complexes, is important for the G2/M transition. Here we identify a modular centrosomal localization signal (CLS) localizing cyclin A to centrosomes independently of Cdk binding. The cyclin A CLS is located in a distinct part of the molecule compared with the cyclin E CLS and includes the MRAIL hydrophobic patch involved in substrate recognition. The cyclin A CLS interacts with p27 KIP1 , and expression of p27 KIP1 removes cyclin A but not cyclin E from centrosomes. Expression of the cyclin A CLS displaces both endogenous cyclin A and E from centrosomes and inhibits DNA replication, supporting an emerging concept that DNA replication is linked to centrosomal events. Structural analysis indicates that differences in surface charge and length of the C-terminal helix explain why the MRAIL region in cyclin E is not a functional CLS. These results indicate that the cyclin A CLS may contribute to targeting and recognition of centrosomal Cdk substrates and is required for specific effects of p27 KIP1 on cyclin A-Cdk2.centrosomal localization signal | p27 KIP1 | cell cycle | hydrophobic patch

show abstract

“…Centrosome function, replication, segregation and structure maintenance depends on regulatory proteins of cell cycle and other cellular signalling pathways [18][19][20][21] . In cancer cells, centrosome morphology and number are frequently dysregulated 22,23 .…”

mentioning

confidence: 99%

LGALS3BP regulates centriole biogenesis and centrosome hypertrophy in cancer cells

et al. 2013

View full text Add to dashboard Cite

Centrosome morphology and number are frequently deregulated in cancer cells. Here, to identify factors that are functionally relevant for centrosome abnormalities in cancer cells, we established a protein-interaction network around 23 centrosomal and cell-cycle regulatory proteins, selecting the interacting proteins that are deregulated in cancer for further studies. One of these components, LGALS3BP, is a centriole-and basal body-associated protein with a dual role, triggering centrosome hypertrophy when overexpressed and causing accumulation of centriolar substructures when downregulated. The cancer cell line SK-BR-3 that overexpresses LGALS3BP exhibits hypertrophic centrosomes, whereas in seminoma tissues with low expression of LGALS3BP, supernumerary centriole-like structures are present. Centrosome hypertrophy is reversed by depleting LGALS3BP in cells endogenously overexpressing this protein, supporting a direct role in centrosome aberration. We propose that LGALS3BP suppresses assembly of centriolar substructures, and when depleted, causes accumulation of centriolar complexes comprising CPAP, acetylated tubulin and centrin.

show abstract

Control At The Cell Center: The Role Of Spindle Poles In Cytoskeletal Organization And Cell Cycle Regulation

Cited by 28 publications

References 57 publications

Functional importance of RASSF1A microtubule localization and polymorphisms

Functional importance of RASSF1A microtubule localization and polymorphisms

Discovery of a distinct domain in cyclin A sufficient for centrosomal localization independently of Cdk binding

LGALS3BP regulates centriole biogenesis and centrosome hypertrophy in cancer cells

Contact Info

Product

Resources

About