Caspase-2, a novel lipid sensor under the control of sterol regulatory element binding protein 2.

Abstract:

: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.

journal_name

Mol Cell Biol

authors

Logette E,Le Jossic-Corcos C,Masson D,Solier S,Sequeira-Legrand A,Dugail I,Lemaire-Ewing S,Desoche L,Solary E,Corcos L

doi

10.1128/MCB.25.21.9621-9631.2005

subject

Has Abstract

pub_date

2005-11-01 00:00:00

pages

9621-31

issue

21

eissn

0270-7306

issn

1098-5549

pii

25/21/9621

journal_volume

25

pub_type

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