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Calcium- and integrin-binding protein 1 regulates microtubule organization and centrosome segregation through polo like kinase 3 during cell cycle progression

Polo-like kinases (Plks) are a family of serine/threonine protein kinases that are involved in the regulation of the various stages of the cell cycle. Plk2 and Plk3, two members of this family, are known to interact with calcium- and integrin-binding protein 1 (CIB1). Activity of both Plk2 and Plk3...

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Published in:The international journal of biochemistry & cell biology 2011-01, Vol.43 (1), p.120-129
Main Authors: Naik, Meghna U., Naik, Ulhas P.
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Naik, Ulhas P.
description Polo-like kinases (Plks) are a family of serine/threonine protein kinases that are involved in the regulation of the various stages of the cell cycle. Plk2 and Plk3, two members of this family, are known to interact with calcium- and integrin-binding protein 1 (CIB1). Activity of both Plk2 and Plk3 is inhibited by CIB1 in a calcium-dependent manner. However, the physiological consequences of this inhibition are not known. Here, we show that overexpression of CIB1 inhibits T47D cell proliferation. Overexpression of CIB1 or knockdown of Plk3 using shRNA produced a multinucleated phenotype in T47D cells. This phenotype was not cancer cell specific, since it also occurred in normal cells. The cells overexpressing CIB1 appear to undergo proper nuclear division, but are unable to complete the process of cytokinesis, thus forming large multinucleated cells. Both CIB1 overexpression and Plk3 knockdown disrupted microtubule organization and centrosomal segregation, which may have led to incomplete cytokinesis. The observed effect of CIB1 overexpression is not due to the inhibition of Plk2 by CIB1. Plk3 and CIB1 both colocalize at the centrosomes, however, localization of CIB1 is dependent on the expression of Plk3. Furthermore, expression of Plk3 blocks the multinucleated phenotype induced by expression of CIB1 in these cells. These results suggest that CIB1 tightly regulates Plk3 activity during cell division and that either over- or underexpression results in a multinucleated phenotype.
doi_str_mv 10.1016/j.biocel.2010.10.003
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subjects Apoptosis - genetics
Calcium - metabolism
Calcium-Binding Proteins - genetics
Calcium-Binding Proteins - metabolism
Cell Cycle - genetics
Cell Line, Tumor
Centrosome - metabolism
Centrosome - ultrastructure
Centrosomes
CIB1
Cytokinesis
Female
Giant Cells - cytology
Giant Cells - metabolism
Humans
Integrins - genetics
Integrins - metabolism
Intracellular Signaling Peptides and Proteins
Microtubules
Microtubules - genetics
Microtubules - metabolism
Microtubules - ultrastructure
Multinucleation
Plk3
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
T47D
title Calcium- and integrin-binding protein 1 regulates microtubule organization and centrosome segregation through polo like kinase 3 during cell cycle progression
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