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The transcriptional repressor Kaiso localizes at the mitotic spindle and is a constituent of the pericentriolar material.

Soubry A, Staes K, Parthoens E, Noppen S, Stove C, Bogaert P, van Hengel J, van Roy F - PLoS ONE (2010)

Bottom Line: In the present study we monitored Kaiso's subcellular localization during the cell cycle and found the following: (1) during interphase, Kaiso is located not only in the nucleus, but also on microtubular structures, including the centrosome; (2) at metaphase, it is present at the centrosomes and on the spindle microtubules; (3) during telophase, it accumulates at the midbody.We found that Kaiso is a genuine PCM component that belongs to a pericentrin molecular complex.Knockdown of Kaiso accelerated cell proliferation.

View Article: PubMed Central - PubMed

Affiliation: Department for Molecular Biomedical Research, VIB, Ghent, Belgium.

ABSTRACT
Kaiso is a BTB/POZ zinc finger protein known as a transcriptional repressor. It was originally identified through its in vitro association with the Armadillo protein p120ctn. Subcellular localization of Kaiso in cell lines and in normal and cancerous human tissues revealed that its expression is not restricted to the nucleus. In the present study we monitored Kaiso's subcellular localization during the cell cycle and found the following: (1) during interphase, Kaiso is located not only in the nucleus, but also on microtubular structures, including the centrosome; (2) at metaphase, it is present at the centrosomes and on the spindle microtubules; (3) during telophase, it accumulates at the midbody. We found that Kaiso is a genuine PCM component that belongs to a pericentrin molecular complex. We analyzed the functions of different domains of Kaiso by visualizing the subcellular distribution of GFP-tagged Kaiso fragments throughout the cell cycle. Our results indicate that two domains are responsible for targeting Kaiso to the centrosomes and microtubules. The first domain, designated SA1 for spindle-associated domain 1, is located in the center of the Kaiso protein and localizes at the spindle microtubules and centrosomes; the second domain, SA2, is an evolutionarily conserved domain situated just before the zinc finger domain and might be responsible for localizing Kaiso towards the centrosomal region. Constructs containing both SA domains and Kaiso's aminoterminal BTB/POZ domain triggered the formation of abnormal centrosomes. We also observed that overexpression of longer or full-length Kaiso constructs led to mitotic cell arrest and frequent cell death. Knockdown of Kaiso accelerated cell proliferation. Our data reveal a new target for Kaiso at the centrosomes and spindle microtubules during mitosis. They also strongly imply that Kaiso's function as a transcriptional regulator might be linked to the control of the cell cycle and to cell proliferation in cancer.

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Hypothetical model for interactions of Kaiso's functional domains at the centrosomes during the onset of mitosis.The Kaiso domains putatively responsible for its localization at the centrosomes or spindle microtubules are shown inside yellow Kaiso balloons. At the G2/M phase, the centrosome consists of a mother and a daughter centriole [drawn according to 44], as well as two growing procentrioles. Centrin (depicted in green) is concentrated in the centriolar distal lumen. MT, microtubules.A role for the SA2 domain of Kaiso: After breakdown of the nuclear envelope, nuclear proteins, such as NuMA, TPX2 and possibly also Kaiso, are released in a RanGTP-dependent manner from complexes containing importin. A fraction of RanGTP is present at the centrosomes throughout the cell cycle and can locally activate these centrosomal factors during G2/M phase; this allows microtubule nucleation and stabilization near the centriole pairs [69]. The molecular Kaiso-pericentrin interaction in the PCM, which is direct or indirect via an adaptor (depicted as ?), might also be a function of the SA2 domain.A role for the SA1 domain: Kaiso might associate either directly with the microtubules or indirectly via the motor protein dynein, along with other centrosomal components such as PCM-1 and ch-TOG.A role for the BTB/POZ domain in the centrosome: The zinc finger protein CTCF might recruit Kaiso towards the centrosomes (or vice versa) via the hetero-dimerization capacities of Kaiso's BTB/POZ domain.
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pone-0009203-g013: Hypothetical model for interactions of Kaiso's functional domains at the centrosomes during the onset of mitosis.The Kaiso domains putatively responsible for its localization at the centrosomes or spindle microtubules are shown inside yellow Kaiso balloons. At the G2/M phase, the centrosome consists of a mother and a daughter centriole [drawn according to 44], as well as two growing procentrioles. Centrin (depicted in green) is concentrated in the centriolar distal lumen. MT, microtubules.A role for the SA2 domain of Kaiso: After breakdown of the nuclear envelope, nuclear proteins, such as NuMA, TPX2 and possibly also Kaiso, are released in a RanGTP-dependent manner from complexes containing importin. A fraction of RanGTP is present at the centrosomes throughout the cell cycle and can locally activate these centrosomal factors during G2/M phase; this allows microtubule nucleation and stabilization near the centriole pairs [69]. The molecular Kaiso-pericentrin interaction in the PCM, which is direct or indirect via an adaptor (depicted as ?), might also be a function of the SA2 domain.A role for the SA1 domain: Kaiso might associate either directly with the microtubules or indirectly via the motor protein dynein, along with other centrosomal components such as PCM-1 and ch-TOG.A role for the BTB/POZ domain in the centrosome: The zinc finger protein CTCF might recruit Kaiso towards the centrosomes (or vice versa) via the hetero-dimerization capacities of Kaiso's BTB/POZ domain.

Mentions: Immunofluorescent colocalization revealed that Kaiso is less focally expressed in the centrosomes than centrin. Evidence for association of Kaiso with the PCM was strengthened by our finding of pericentrin and ©-tubulin in a molecular complex with Kaiso. PCM is a structurally intricate protein complex consisting of a lattice of large coiled coil proteins, including pericentrin and AKAP-450 [44], [45] (Fig. 13). Interestingly, pericentrin associates with γ-tubulin to form a complex that controls spindle organization and mitotic entry [29]. Moreover, pericentrin interacts with many other structural and regulatory proteins (reviewed in [41]), including the chromatin remodeling proteins CHD3 and CHD4 [46]. Inactivating mutations of pericentrin lead to cell cycle checkpoint and microtubule organization defects, resulting in mitotic arrest, dwarfism and ciliopathies, whereas pericentrin overexpression is seen in cancers and correlates with chromosomal instability (reviewed in [41]). The occurrence of Kaiso, a transcriptional repressor, as a novel pericentrin interactor suggests an intriguing regulatory role for both pericentrin and Kaiso, but the details of this interaction await further study.


The transcriptional repressor Kaiso localizes at the mitotic spindle and is a constituent of the pericentriolar material.

Soubry A, Staes K, Parthoens E, Noppen S, Stove C, Bogaert P, van Hengel J, van Roy F - PLoS ONE (2010)

Hypothetical model for interactions of Kaiso's functional domains at the centrosomes during the onset of mitosis.The Kaiso domains putatively responsible for its localization at the centrosomes or spindle microtubules are shown inside yellow Kaiso balloons. At the G2/M phase, the centrosome consists of a mother and a daughter centriole [drawn according to 44], as well as two growing procentrioles. Centrin (depicted in green) is concentrated in the centriolar distal lumen. MT, microtubules.A role for the SA2 domain of Kaiso: After breakdown of the nuclear envelope, nuclear proteins, such as NuMA, TPX2 and possibly also Kaiso, are released in a RanGTP-dependent manner from complexes containing importin. A fraction of RanGTP is present at the centrosomes throughout the cell cycle and can locally activate these centrosomal factors during G2/M phase; this allows microtubule nucleation and stabilization near the centriole pairs [69]. The molecular Kaiso-pericentrin interaction in the PCM, which is direct or indirect via an adaptor (depicted as ?), might also be a function of the SA2 domain.A role for the SA1 domain: Kaiso might associate either directly with the microtubules or indirectly via the motor protein dynein, along with other centrosomal components such as PCM-1 and ch-TOG.A role for the BTB/POZ domain in the centrosome: The zinc finger protein CTCF might recruit Kaiso towards the centrosomes (or vice versa) via the hetero-dimerization capacities of Kaiso's BTB/POZ domain.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2821401&req=5

pone-0009203-g013: Hypothetical model for interactions of Kaiso's functional domains at the centrosomes during the onset of mitosis.The Kaiso domains putatively responsible for its localization at the centrosomes or spindle microtubules are shown inside yellow Kaiso balloons. At the G2/M phase, the centrosome consists of a mother and a daughter centriole [drawn according to 44], as well as two growing procentrioles. Centrin (depicted in green) is concentrated in the centriolar distal lumen. MT, microtubules.A role for the SA2 domain of Kaiso: After breakdown of the nuclear envelope, nuclear proteins, such as NuMA, TPX2 and possibly also Kaiso, are released in a RanGTP-dependent manner from complexes containing importin. A fraction of RanGTP is present at the centrosomes throughout the cell cycle and can locally activate these centrosomal factors during G2/M phase; this allows microtubule nucleation and stabilization near the centriole pairs [69]. The molecular Kaiso-pericentrin interaction in the PCM, which is direct or indirect via an adaptor (depicted as ?), might also be a function of the SA2 domain.A role for the SA1 domain: Kaiso might associate either directly with the microtubules or indirectly via the motor protein dynein, along with other centrosomal components such as PCM-1 and ch-TOG.A role for the BTB/POZ domain in the centrosome: The zinc finger protein CTCF might recruit Kaiso towards the centrosomes (or vice versa) via the hetero-dimerization capacities of Kaiso's BTB/POZ domain.
Mentions: Immunofluorescent colocalization revealed that Kaiso is less focally expressed in the centrosomes than centrin. Evidence for association of Kaiso with the PCM was strengthened by our finding of pericentrin and ©-tubulin in a molecular complex with Kaiso. PCM is a structurally intricate protein complex consisting of a lattice of large coiled coil proteins, including pericentrin and AKAP-450 [44], [45] (Fig. 13). Interestingly, pericentrin associates with γ-tubulin to form a complex that controls spindle organization and mitotic entry [29]. Moreover, pericentrin interacts with many other structural and regulatory proteins (reviewed in [41]), including the chromatin remodeling proteins CHD3 and CHD4 [46]. Inactivating mutations of pericentrin lead to cell cycle checkpoint and microtubule organization defects, resulting in mitotic arrest, dwarfism and ciliopathies, whereas pericentrin overexpression is seen in cancers and correlates with chromosomal instability (reviewed in [41]). The occurrence of Kaiso, a transcriptional repressor, as a novel pericentrin interactor suggests an intriguing regulatory role for both pericentrin and Kaiso, but the details of this interaction await further study.

Bottom Line: In the present study we monitored Kaiso's subcellular localization during the cell cycle and found the following: (1) during interphase, Kaiso is located not only in the nucleus, but also on microtubular structures, including the centrosome; (2) at metaphase, it is present at the centrosomes and on the spindle microtubules; (3) during telophase, it accumulates at the midbody.We found that Kaiso is a genuine PCM component that belongs to a pericentrin molecular complex.Knockdown of Kaiso accelerated cell proliferation.

View Article: PubMed Central - PubMed

Affiliation: Department for Molecular Biomedical Research, VIB, Ghent, Belgium.

ABSTRACT
Kaiso is a BTB/POZ zinc finger protein known as a transcriptional repressor. It was originally identified through its in vitro association with the Armadillo protein p120ctn. Subcellular localization of Kaiso in cell lines and in normal and cancerous human tissues revealed that its expression is not restricted to the nucleus. In the present study we monitored Kaiso's subcellular localization during the cell cycle and found the following: (1) during interphase, Kaiso is located not only in the nucleus, but also on microtubular structures, including the centrosome; (2) at metaphase, it is present at the centrosomes and on the spindle microtubules; (3) during telophase, it accumulates at the midbody. We found that Kaiso is a genuine PCM component that belongs to a pericentrin molecular complex. We analyzed the functions of different domains of Kaiso by visualizing the subcellular distribution of GFP-tagged Kaiso fragments throughout the cell cycle. Our results indicate that two domains are responsible for targeting Kaiso to the centrosomes and microtubules. The first domain, designated SA1 for spindle-associated domain 1, is located in the center of the Kaiso protein and localizes at the spindle microtubules and centrosomes; the second domain, SA2, is an evolutionarily conserved domain situated just before the zinc finger domain and might be responsible for localizing Kaiso towards the centrosomal region. Constructs containing both SA domains and Kaiso's aminoterminal BTB/POZ domain triggered the formation of abnormal centrosomes. We also observed that overexpression of longer or full-length Kaiso constructs led to mitotic cell arrest and frequent cell death. Knockdown of Kaiso accelerated cell proliferation. Our data reveal a new target for Kaiso at the centrosomes and spindle microtubules during mitosis. They also strongly imply that Kaiso's function as a transcriptional regulator might be linked to the control of the cell cycle and to cell proliferation in cancer.

Show MeSH
Related in: MedlinePlus