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Mol Cell Biol, July 1998, p. 4272-4281, Vol. 18, No. 7
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Calcium and S100B Regulation of p53-Dependent Cell Growth Arrest and Apoptosis

Christian Scotto,1 Jean Christophe Deloulme,1 Denis Rousseau,2 Edmond Chambaz,1 and Jacques Baudier1 *

Département de Biologie Moléculaire et Structurale du CEA, DBMS-BRCE INSERM Unité 244,1 and Institut de Biologie Structurale J. P. Ebel, CEN-G,2 38054 Grenoble Cedex 9, France

Received 11 February 1998/Returned for modification 20 March 1998/Accepted 20 April 1998

In glial C6 cells constitutively expressing wild-type p53, synthesis of the calcium-binding protein S100B is associated with cell density-dependent inhibition of growth and apoptosis in response to UV irradiation. A functional interaction between S100B and p53 was first demonstrated in p53-negative mouse embryo fibroblasts (MEF cells) by sequential transfection with the S100B and the temperature-sensitive p53Val135 genes. We show that in MEF cells expressing a low level of p53Val135, S100B cooperates with p53Val135 in triggering calcium-dependent cell growth arrest and cell death in response to UV irradiation at the nonpermissive temperature (37.5°C). Calcium-dependent growth arrest of MEF cells expressing S100B correlates with specific nuclear accumulation of the wild-type p53Val135 conformational species. S100B modulation of wild-type p53Val135 nuclear translocation and functions was confirmed with the rat embryo fibroblast (REF) cell line clone 6, which is transformed by oncogenic Ha-ras and overexpression of p53Val135. Ectopic expression of S100B in clone 6 cells restores contact inhibition of growth at 37.5°C, which also correlates with nuclear accumulation of the wild-type p53Val135 conformational species. Moreover, a calcium ionophore mediates a reversible G1 arrest in S100B-expressing REF (S100B-REF) cells at 37.5°C that is phenotypically indistinguishable from p53-mediated G1 arrest at the permissive temperature (32°C). S100B-REF cells proceeding from G1 underwent apoptosis in response to UV irradiation. Our data support a model in which calcium signaling and S100B cooperate with the p53 pathways of cell growth inhibition and apoptosis.

* Corresponding author. Mailing address: INSERM Unité 244, DBMS-BRCE, Grenoble Cedex 9, France. Phone: (33) 476 88 43 28. Fax: (33) 476 88 51 00. E-mail: Jacquo{at}hofn.ceng.cea.fr.

Mol Cell Biol, July 1998, p. 4272-4281, Vol. 18, No. 7
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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