1. Academic Validation
  2. Expression of the Calcium-Binding Protein CALB1 Is Induced and Controls Intracellular Ca2+ Levels in Senescent Cells

Expression of the Calcium-Binding Protein CALB1 Is Induced and Controls Intracellular Ca2+ Levels in Senescent Cells

  • Int J Mol Sci. 2022 Aug 19;23(16):9376. doi: 10.3390/ijms23169376.
Clotilde Raynard 1 Nolwenn Tessier 2 Anda Huna 1 Marine Warnier 1 Jean-Michel Flaman 1 Fabien Van Coppenolle 2 Sylvie Ducreux 2 Nadine Martin 1 David Bernard 1
Affiliations

Affiliations

  • 1 Centre de Recherche en Cancérologie de Lyon, Inserm U1052, CNRS UMR 5286, Centre Léon Bérard, Université de Lyon, 69373 Lyon, France.
  • 2 CarMeN Laboratory, INSERM, INRA, INSA Lyon, Université Claude Bernard Lyon 1, 69500 Bron, France.
Abstract

In response to many stresses, such as oncogene activation or DNA damage, cells can enter cellular senescence, a state of proliferation arrest accompanied by a senescence-associated secretory phenotype (SASP). Cellular senescence plays a key role in many physiopathological contexts, including Cancer, aging and aging-associated diseases, therefore, it is critical to understand how senescence is regulated. Calcium ions (CA2+) recently emerged as pivotal regulators of cellular senescence. However, how CA2+ levels are controlled during this process is barely known. Here, we report that intracellular CA2+ contents increase in response to many senescence inducers in immortalized human mammary epithelial cells (HMECs) and that expression of calbindin 1 (CALB1), a CA2+-binding protein, is upregulated in this context, through the CA2+-dependent Calcineurin/NFAT pathway. We further show that overexpression of CALB1 buffers the rise in intracellular CA2+ levels observed in senescent cells. Finally, we suggest that increased expression of CA2+-binding proteins calbindins is a frequent mark of senescent cells. This work thus supports that, together with CA2+channels, CA2+-binding proteins modulate CA2+ levels and flux during cellular senescence. This opens potential avenues of research to better understand the role of CA2+ and of CA2+-binding proteins in regulating cellular senescence.

Keywords

CALB1; Ca2+; NFAT; cellular senescence.

Figures
Products