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Molecular and Cellular Biology, November 2005, p. 9621-9631, Vol. 25, No. 21
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.21.9621-9631.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Caspase-2, a Novel Lipid Sensor under the Control of Sterol Regulatory Element Binding Protein 2

E. Logette,¹ C. Le Jossic-Corcos,^2, D. Masson,³ S. Solier,¹ A. Sequeira-Legrand,¹ I. Dugail,⁴ S. Lemaire-Ewing,³ L. Desoche,¹ E. Solary,¹ and L. Corcos^1*

INSERM U517, IFR100, Faculté de Médecine, 7 bd. Jeanne of Arc, 21000 Dijon, France,¹ Laboratoire de Biologie Moléculaire et Cellulaire, Faculté des Sciences Gabriel, 6 bd. Gabriel, 21000 Dijon, France,² INSERM U498, IFR100, CHRU le Bocage, 7 bd. Jeanne of Arc, 21000 Dijon, France,³ INSERM U465, Centre des Cordeliers, 15 rue de l'Ecole de Médecine, 75270 Paris, France⁴

Received 22 April 2005/ Returned for modification 18 May 2005/ Accepted 16 August 2005

Caspases play important roles in apoptotic cell death and in some other functions, such as cytokine maturation, inflammation, or differentiation. We show here that the 5'-flanking region of the human CASP-2 gene contains three functional response elements for sterol regulatory element binding proteins (SREBPs), proteins that mediate the transcriptional activation of genes involved in cholesterol, triacylglycerol, and fatty acid synthesis. Exposure of several human cell lines to statins, lipid-lowering drugs that drive SREBP proteolytic activation, induced the CASP-2 gene to an extent similar to that for known targets of SREBP proteins. Adenoviral vector-mediated transfer of active SREBP-2 also induced expression of the CASP-2 gene and the caspase-2 protein and increased the cholesterol and triacylglycerol cellular content. These rises in lipids were strongly impaired following small interfering RNA-mediated silencing of the CASP-2 gene. Taken together, our results identify the human CASP-2 gene as a member of the SREBP-responsive gene battery that senses lipid levels in cells and raise the possibility that caspase-2 participates in the control of cholesterol and triacylglycerol levels.

Supplemental material for this article may be found at http://mcb.asm.org/.

Present address: EA948, Faculté de Médecine, 22 avenue Camille Desmoulins, 29238 Brest Cedex 3, France.

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