Caspase-1ζ, a new splice variant of the caspase-1 gene

Feng, Qi Sheng; Pei-xiang, LI; Leung, Peter C.K.; Auersperg, Nelly

doi:10.1016/j.ygeno.2004.06.005

Cited by 20 publications

(17 citation statements)

References 20 publications

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“…However, caspase-1 also plays an important role in apoptosis, particularly under certain pathologic conditions such as neurodegenerative disorders and hypoxic ischemia (5,6). Recent data from our lab showed that overexpression of caspase-1a in HEK293 cells causes apoptosis, which is dependent on its catalytic effect (7). Not only the full-length a isoform, but a newly found NH 2 -terminal truncated isoform~is also able to induce apoptosis in 293 cells.…”

Section: Discussionmentioning

confidence: 97%

“…Full-length CASP1 cDNA was obtained by reverse transcription-PCR from human OSE cDNA as described previously (7). To create a mutant at the epicenter of caspase-1 QACRG location, site-directed mutation of the caspase-1a plasmid were carried out by BioS&T (Montreal, Quebec), so that Cys285 was replaced by serine.…”

Section: Methodsmentioning

confidence: 99%

“…Alternative splicing of this gene results in six transcript variants encoding distinct isoforms. Some of these, including caspase-1~, which was recently identified by us, are capable of inducing apoptosis in cultured cells, e.g., in line HEK293, and this effect is specifically dependent on the catalytic activity of caspase-1 (7). The predominant isoform in most human tissues is caspase-1a (7).…”

Section: Introductionmentioning

confidence: 98%

“…Some of these, including caspase-1~, which was recently identified by us, are capable of inducing apoptosis in cultured cells, e.g., in line HEK293, and this effect is specifically dependent on the catalytic activity of caspase-1 (7). The predominant isoform in most human tissues is caspase-1a (7). Emerging evidence suggests that during the apoptotic response of macrophages to microbial infection, caspase-1 activation is initiated by the formation of a protein complex similar to an apoptosome, containing the cytoplasmic proteins NALP1, ASC, and caspase-5 (8).…”

Section: Introductionmentioning

confidence: 99%

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Caspase-1α Is Down-regulated in Human Ovarian Cancer Cells and the Overexpression of Caspase-1α Induces Apoptosis

et al. 2005

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Caspase-1 plays a key role in the processing of cytokines and in the apoptosis of neurons and macrophages. Whether it also causes apoptosis of cancer cells has been unclear. In this study, we screened an array of apoptosis-related proteins in ovarian carcinoma cell lines and their tissue of origin, ovarian surface epithelium (OSE). Caspase-1A protein was abundant in OSE and in nontumorigenic OSE with extended but limited life spans (immortalized OSE), but was reduced in the cancer lines A2780 and OVCAR10. By Western blot and immunofluorescence, caspase-1A levels were greatly reduced in six of eight ovarian carcinoma lines compared with OSE. By realtime reverse transcription-PCR, steady-state transcripts of the CASP1 gene were proportional to protein levels. Caspase-1A overexpression caused significant apoptosis, but overexpression of a caspase-1A mutant without catalytic activity did not, confirming that the effect was caspase-1A-specific. Immunofluorescence of caspase-1A and terminal nucleotidyl transferase-mediated dUTP-X nick end labeling colocalization clearly established a link between apoptosis and caspase-1A expression. Caspase-9 and caspase-3 were activated in caspase-1A overexpressing A2780 cells, suggesting involvement of an intrinsic apoptotic pathway. Caspase-1A overexpression did not change the apoptotic effect of cisplatin in A2780 and OVCAR10 cells, suggesting that this agent activates a different pathway. Immunohistochemically, caspase-1 was lower in ovarian serous carcinomas than in OSE. Our study indicates, for the first time, that caspase-1A is proapoptotic in ovarian cancer cells, and raises the possibility that its downregulation is one of the mechanisms which increase resistance to apoptosis in cancer cells. (Cancer Res 2005; 65(19): 8591-6)

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Section: Discussionmentioning

confidence: 97%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Caspase-1α Is Down-regulated in Human Ovarian Cancer Cells and the Overexpression of Caspase-1α Induces Apoptosis

et al. 2005

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“…Our expression array data demonstrate that MMSET knockdown up-regulated the expression of several genes, such as CASP1, CASP4 and FOXO3A, whose overexpression triggers programmed cell death in human cells. 27,28 In addition, FOXO3A responds to cellular stress by inducing cell cycle arrest, repair of damaged DNA and apoptosis. [29][30][31] In myeloma cells, FOXO3A is a direct target of the antiapoptotic AKT of the PI3K pathway that plays an important role in the survival of myeloma cells by preventing the nuclear translocation and activation of pro-apoptotic proteins such as Bim and Fas ligands.…”

Section: Genementioning

confidence: 99%

MMSET deregulation affects cell cycle progression and adhesion regulons in t(4;14) myeloma plasma cells

Brito¹,

Walker²,

Jenner³

et al. 2009

Haematologica

112

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BackgroundThe recurrent immunoglobulin translocation, t(4;14)(p16;q32) occurs in 15% of multiple myeloma patients and is associated with poor prognosis, through an unknown mechanism. The t(4;14) up-regulates fibroblast growth factor receptor 3 (FGFR3) and multiple myeloma SET domain (MMSET) genes. The involvement of MMSET in the pathogenesis of t(4;14) multiple myeloma and the mechanism or genes deregulated by MMSET upregulation are still unclear. Design and MethodsThe expression of MMSET was analyzed using a novel antibody. The involvement of MMSET in t(4;14) myelomagenesis was assessed by small interfering RNA mediated knockdown combined with several biological assays. In addition, the differential gene expression of MMSET-induced knockdown was analyzed with expression microarrays. MMSET gene targets in primary patient material was analyzed by expression microarrays. ResultsWe found that MMSET isoforms are expressed in multiple myeloma cell lines, being exclusively up-regulated in t(4;14)-positive cells. Suppression of MMSET expression affected cell proliferation by both decreasing cell viability and cell cycle progression of cells with the t(4;14) translocation. These findings were associated with reduced expression of genes involved in the regulation of cell cycle progression (e.g. CCND2, CCNG1, BRCA1, AURKA and CHEK1), apoptosis (CASP1, CASP4 and FOXO3A) and cell adhesion (ADAM9 and DSG2). Furthermore, we identified genes involved in the latter processes that were differentially expressed in t(4;14) multiple myeloma patient samples. ConclusionsIn conclusion, dysregulation of MMSET affects the expression of several genes involved in the regulation of cell cycle progression, cell adhesion and survival.

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Alternative Pre-mRNA Splicing, Cell Death, and Cancer

Kong

Ray

Yang

et al. 2013

Cancer Treatment and Research

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Alternative splicing is one of the most powerful mechanisms for generating functionally distinct products from a single genetic loci and for fine-tuning gene activities at the post-transcriptional level. Alternative splicing plays important roles in regulating genes critical for cell death. These cell death genes encode death ligands, cell surface death receptors, intracellular death regulators, signal transduction molecules, and death executor enzymes such as caspases and nucleases. Alternative splicing of these genes often leads to the formation of functionally different products, some of which have antagonistic effects that are either cell death-promoting or cell death-preventing. Differential alternative splicing can affect expression, subcellular distribution, and functional activities of the gene products. Molecular defects in splicing regulation of cell death genes have been associated with cancer development and resistance to treatment. Studies using molecular, biochemical, and systems-based approaches have begun to reveal mechanisms underlying the regulation of alternative splicing of cell death genes. Systematic studies have begun to uncover the multi-level interconnected networks that regulate alternative splicing. A global picture of the complex mechanisms that regulate cell death genes at the pre-mRNA splicing level has thus begun to emerge.

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Caspase-1ζ, a new splice variant of the caspase-1 gene

Cited by 20 publications

References 20 publications

Caspase-1α Is Down-regulated in Human Ovarian Cancer Cells and the Overexpression of Caspase-1α Induces Apoptosis

Caspase-1α Is Down-regulated in Human Ovarian Cancer Cells and the Overexpression of Caspase-1α Induces Apoptosis

MMSET deregulation affects cell cycle progression and adhesion regulons in t(4;14) myeloma plasma cells

Alternative Pre-mRNA Splicing, Cell Death, and Cancer

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