Nucleoplasmic calcium is required for cell proliferation.
Ca(2+) signals regulate cell proliferation, but the spatial and temporal specificity of these signals is unknown. Here we use selective buffers of nucleoplasmic or cytoplasmic Ca(2+) to determine that cell proliferation depends upon Ca(2+) signals within the nucleus rather than in the cytoplasm. Nuclear Ca(2+) signals stimulate cell growth rather than inhibit apoptosis and specifically permit cells to advance through early prophase. Selective buffering of nuclear but not cytoplasmic Ca(2+) signals also impairs growth of tumors in vivo. These findings reveal a major physiological and potential pathophysiological role for nucleoplasmic Ca(2+) signals and suggest that this information can be used to design novel therapeutic strategies to regulate conditions of abnormal cell growth.
Rodrigues
Michele A
MA
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8019, USA.
Gomes
Dawidson A
DA
Leite
M Fatima
MF
Grant
Wayne
W
Zhang
Lei
L
Lam
Wing
W
Cheng
Yung-Chi
YC
Bennett
Anton M
AM
Nathanson
Michael H
MH
D000818:Animals; D002118:Calcium / Q000502:physiology*; D020013:Calcium Signaling; D002453:Cell Cycle; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008938:Mitosis
D002118:Calcium