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A splice variant of ASC regulates IL-1beta release and aggregates differently from intact ASC.

Matsushita K, Takeoka M, Sagara J, Itano N, Kurose Y, Nakamura A, Taniguchi S - Mediators Inflamm. (2009)

Bottom Line: The apoptosis-associated speck-like protein containing a caspase recruit domain (ASC) is involved in apoptosis and innate immunity and is a major adaptor molecule responsible for procaspase-1 activation.Both fASC and vASC were found to activate procaspase-1 to a similar degree, but the efficiency of IL-1beta excretion was significantly higher for vASC.These results suggest that although the PGR domain is dispensable for procaspase-1 activation, it plays an important role in the regulation of the molecular structure and activity of ASC.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Oncology, Institute on Aging and Adaptation, Graduate School of Medicine, Shinshu University, Negano 390-8621, Japan.

ABSTRACT
The apoptosis-associated speck-like protein containing a caspase recruit domain (ASC) is involved in apoptosis and innate immunity and is a major adaptor molecule responsible for procaspase-1 activation. ASC mRNA is encoded by three exons: exons 1 and 3 encode a pyrin domain (PYD) and caspase recruit domain (CARD), respectively, and exon 2 encodes a proline and glycine-rich (PGR) domain. Here, we identified a variant ASC protein (vASC) lacking the PGR domain that was smaller than full length ASC (fASC) derived from fully transcribed mRNA and searched for differences in biochemical and biological nature. Both fASC and vASC were found to activate procaspase-1 to a similar degree, but the efficiency of IL-1beta excretion was significantly higher for vASC. There was also a marked structural difference observed in the fibrous aggregates formed by fASC and vASC. These results suggest that although the PGR domain is dispensable for procaspase-1 activation, it plays an important role in the regulation of the molecular structure and activity of ASC.

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Intracellular distribution of fASC and vASC in Cos7 cells. Expression vectors of fASC or vASC were transfected into Cos7 cells. (a), (d): aggregation of fASC and vASC, scale bar: 30 μM. (b), (e): magnified pictures of (a) and (d), scale bar: 5 μM. (c), (f): aggregations with nuclei, scale bar: 5 μM.
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fig5: Intracellular distribution of fASC and vASC in Cos7 cells. Expression vectors of fASC or vASC were transfected into Cos7 cells. (a), (d): aggregation of fASC and vASC, scale bar: 30 μM. (b), (e): magnified pictures of (a) and (d), scale bar: 5 μM. (c), (f): aggregations with nuclei, scale bar: 5 μM.

Mentions: The distribution of exogenously transfected gene products was examined in Cos7 cells. Both products were seen to form fibrous aggregates (Figure 5), but fASC formed typical circular fibrous aggregates whereas those of vASC were branched; almost 40% of fASC-expressing cells exhibited a diffused fASC pattern and 60% of cells formed circular fibrous aggregates, but vASC formed branched fibrous aggregates in all cells expressing it.


A splice variant of ASC regulates IL-1beta release and aggregates differently from intact ASC.

Matsushita K, Takeoka M, Sagara J, Itano N, Kurose Y, Nakamura A, Taniguchi S - Mediators Inflamm. (2009)

Intracellular distribution of fASC and vASC in Cos7 cells. Expression vectors of fASC or vASC were transfected into Cos7 cells. (a), (d): aggregation of fASC and vASC, scale bar: 30 μM. (b), (e): magnified pictures of (a) and (d), scale bar: 5 μM. (c), (f): aggregations with nuclei, scale bar: 5 μM.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2744265&req=5

fig5: Intracellular distribution of fASC and vASC in Cos7 cells. Expression vectors of fASC or vASC were transfected into Cos7 cells. (a), (d): aggregation of fASC and vASC, scale bar: 30 μM. (b), (e): magnified pictures of (a) and (d), scale bar: 5 μM. (c), (f): aggregations with nuclei, scale bar: 5 μM.
Mentions: The distribution of exogenously transfected gene products was examined in Cos7 cells. Both products were seen to form fibrous aggregates (Figure 5), but fASC formed typical circular fibrous aggregates whereas those of vASC were branched; almost 40% of fASC-expressing cells exhibited a diffused fASC pattern and 60% of cells formed circular fibrous aggregates, but vASC formed branched fibrous aggregates in all cells expressing it.

Bottom Line: The apoptosis-associated speck-like protein containing a caspase recruit domain (ASC) is involved in apoptosis and innate immunity and is a major adaptor molecule responsible for procaspase-1 activation.Both fASC and vASC were found to activate procaspase-1 to a similar degree, but the efficiency of IL-1beta excretion was significantly higher for vASC.These results suggest that although the PGR domain is dispensable for procaspase-1 activation, it plays an important role in the regulation of the molecular structure and activity of ASC.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Oncology, Institute on Aging and Adaptation, Graduate School of Medicine, Shinshu University, Negano 390-8621, Japan.

ABSTRACT
The apoptosis-associated speck-like protein containing a caspase recruit domain (ASC) is involved in apoptosis and innate immunity and is a major adaptor molecule responsible for procaspase-1 activation. ASC mRNA is encoded by three exons: exons 1 and 3 encode a pyrin domain (PYD) and caspase recruit domain (CARD), respectively, and exon 2 encodes a proline and glycine-rich (PGR) domain. Here, we identified a variant ASC protein (vASC) lacking the PGR domain that was smaller than full length ASC (fASC) derived from fully transcribed mRNA and searched for differences in biochemical and biological nature. Both fASC and vASC were found to activate procaspase-1 to a similar degree, but the efficiency of IL-1beta excretion was significantly higher for vASC. There was also a marked structural difference observed in the fibrous aggregates formed by fASC and vASC. These results suggest that although the PGR domain is dispensable for procaspase-1 activation, it plays an important role in the regulation of the molecular structure and activity of ASC.

Show MeSH