Hela /-CaD undergoes a DNA replication-associated switch in localization from the cytoplasm to the nuclei of endothelial cells/endothelial progenitor cells in human tumor vasculature.
Caldesmon (CaD) is a major actin-binding protein distributed in a variety of cell types. So far no diversity in functions of the different isoforms were found in in vitro studies. The low molecular weight isoform (Hela /-CaD) was detected in the vasculature of a variety of tumor types in our previous study. Proliferation of endothelial cells/endothelial progenitor cells (ECs/EPCs) is a crucial event for formation of new blood vessels. Here we report the intranuclear translocation of Hela /-CaD in cell cycle activated ECs/EPCs in the vasculature of human tumors. The nuclear translocation coincides with phosphorylation of the molecule and the activation of intranuclear protein kinase p34(cdc2). These findings point to a function of this molecule relating to DNA synthesis which is triggered by cell-cycle signalling pathways. The data challenge and update the generally accepted concept that CaD is a pure cytoplasmic protein in vitro study. It suggests that nuclear translocation of Hela /-CaD serves as an additional regulatory step in the control of mitotic initiation and triggers further investigations in the role of this protein in the regulation of nuclear investigations in the role of this protein in the regulation of nuclear functions.
Zheng
Ping-Pin
PP
Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands.
Weiden
M van der
Mv
Sillevis Smitt
Peter A E
PA
Luider
Theo M
TM
Kros
Johan M
JM
D001921:Brain / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism; D004261:DNA Replication; D042783:Endothelial Cells / Q000166:cytology; D006801:Humans; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D020033:Protein Isoforms; D021381:Protein Transport; D013234:Stem Cells / Q000166:cytology
D002148:Calmodulin-Binding Proteins; D020033:Protein Isoforms