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Alteration in temporal kinetics of Ca 2+ signaling and control of growth and proliferation
Author(s) -
Lipskaia Larissa,
Lompré AnneMarie
Publication year - 2004
Publication title -
biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 85
eISSN - 1768-322X
pISSN - 0248-4900
DOI - 10.1016/j.biolcel.2003.11.001
Subject(s) - nfat , microbiology and biotechnology , biology , calcium signaling , ryanodine receptor , creb , transcription factor , calcium , signal transduction , voltage dependent calcium channel , second messenger system , calcium in biology , endoplasmic reticulum , calcium atpase , serca , intracellular , biochemistry , atpase , chemistry , enzyme , gene , organic chemistry
Calcium is a ubiquitous second messenger controlling a broad range of cellular functions including growth and proliferation. Quiescent, hyperthrophic and proliferating cells have different types of calcium signal. In quiescent cells the calcium signal mostly involves elementary calcium events such as sparks and puffs, produced by localized Ca 2+ release via a cluster of intracellular calcium channels, IP3 receptors and ryanodine receptors. This type of calcium signal promotes activation of the transcription factor CREB (cAMP response element binding protein) leading to cell cycle arrest in G1 phase via transactivation of p53/p21 signaling pathways. Proliferation is induced by phosphoinositide‐coupled agonists and is associated with a sustained increase in cytosolic calcium due to 1.) enhanced excitability of IP3Rs after IP3 binding; 2.) enhanced activity of store‐operated Ca 2+ channels and T‐type voltage‐operated Ca 2+ channels; 3.) decreased cytosolic Ca 2+ removal due to inhibition of PMCA (plasma membrane Ca 2+ ‐ATPase) and SERCA (sarco/endoplasmic reticulum Ca 2+ ‐ATPase) calcium pumps. This type of calcium signal favors activation of the transcription factor NFAT (nuclear factor of activated T lymphocytes) that promotes hypertrophic growth and/or cell cycle progression. We suggest that the two main Ca 2+ ‐regulated transcription factors, CREB and NFAT, exert opposite control over cell growth and/or proliferation. Therapeutic strategies based on lowering intracellular Ca 2+ or targeting of Ca 2+ ‐regulated transcription factors seems to be a promising approach to arrest growth and/or proliferation.