Alteration in temporal kinetics of Ca²⁺ signaling and control of growth and proliferation

• Larissa Lipskaia

• Anne‐Marie Lompré

Abstract

Abstract 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.

Journal

• Biology of the Cell

  Biology of the Cell 96 (1), 55-68, 2004-02

  Wiley

Keywords

• Cell Biology
• General Medicine

Details

• CRID: 1361418520736229248
• NII Article ID: 30009848227
• DOI: 10.1016/j.biolcel.2003.11.001
• ISSN: 1768322X
• ISSN: 02484900
• Web Site: https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1016%2Fj.biolcel.2003.11.001
• Web Site: https://onlinelibrary.wiley.com/doi/pdf/10.1016/j.biolcel.2003.11.001
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