Nonsense-mediated mRNA decay among human caspases: the caspase-2S putative protein is encoded by an extremely short-lived mRNA.
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Caspase 2↗
Biomedical subjects
S Solier
Publications and source records attributed to S Solier.
Caspase-2, a novel lipid sensor under the control of sterol regulatory element binding protein 2.
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.
5' Flanking Region↗
[Thalidomide with or without dexamethasone for refractory multiple myeloma].
It was shown in 1999 thalidomide could induce a therapeutic response in patients with refractory multiple myeloma. Between March 2000 and January 2002, we treated 21 patients with refractory multiple myeloma with thalidomide (Thalidomide) at initial dose of 400 mg a day. Response rate (Intergroupe Francophone du Myélome criteria) was 33 percent and median progression-free survival estimated to 15 months. All patients suffered from drowsiness and constipation requiring lowest doses. Five patients developed a sensitive neuropathy. Eight refractory patients were treated by a combination of their prior maximally tolerated dose of thalidomide and monthly dexamethasone (Soludécadron) alone (n = 4) or associated to cyclophosphamide (Endoxan) and étoposide (Etopophos) (n = 4). Six patients on 8 were responders. Our results suggest that the combination thalidomide/dexamethasone should be compared to thalidomide alone in a prospective, randomized study in patients with refractory multiple myeloma.
Adult↗