Nucleoplasmic calcium signaling and cell proliferation: calcium signaling in the nucleus

Calcium (Ca(2+)) is an essential signal transduction element involved in the regulation of several cellular activities and it is required at various key stages of the cell cycle. Intracellular Ca(2+) is crucial for the orderly cell cycle progression and plays a vital role in the regulation of cell proliferation. Recently, it was demonstrated by in vitro and in vivo studies that nucleoplasmic Ca(2+) regulates cell growth. Even though the mechanism by which nuclear Ca(2+) regulates cell proliferation is not completely understood, there are reports demonstrating that activation of tyrosine kinase receptors (RTKs) leads to translocation of RTKs to the nucleus to generate localized nuclear Ca(2+) signaling which are believed to modulate cell proliferation. Moreover, nuclear Ca(2+) regulates the expression of genes involved in cell growth. This review will describe the nuclear Ca(2+) signaling machinery and its role in cell proliferation. Additionally, the potential role of nuclear Ca(2+) as a target in cancer therapy will be discussed.