A Splice Variant of ASC Regulates IL-1β Release and Aggregates Differently from Intact ASC

被引：27

作者：

Matsushita, Kazuhiko ^{[1
]}

Takeoka, Michiko ^{[1
]}

Sagara, Junji ^{[2
]}

Itano, Naoki ^{[1
]}

Kurose, Yuka ^{[1
]}

Nakamura, Akihiro ^{[3
]}

Taniguchi, Shun'ichiro ^{[1
]}

机构：

[1] Shinshu Univ, Grad Sch Med, Inst Aging & Adaptat, Dept Mol Oncol, Negano 3908621, Japan

[2] Shinshu Univ, Dept Biomed Lab Sci, Matsumoto, Nagano 3908621, Japan

[3] Keio Univ, Inst Adv Biosci, Tsuruoka, Yamagata 9970017, Japan

来源：

MEDIATORS OF INFLAMMATION | 2009年 / 2009卷

关键词：

CASPASE RECRUITMENT DOMAIN; SPECK-LIKE PROTEIN; INFLAMMATORY CASPASES; PYRIN DOMAIN; APOPTOSIS; ACTIVATION; OLIGOMERIZATION; PYROPTOSOME; RESIDUES; PEPTIDE;

D O I：

10.1155/2009/287387

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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-1 beta 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. Copyright (C) 2009 Kazuhiko Matsushita et al.

引用

页数：6

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