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Mediators of Inflammation
Volume 2009, Article ID 287387, 6 pages
Research Article

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

1Department of Molecular Oncology, Institute on Aging and Adaptation, Graduate School of Medicine, Shinshu University, Negano 390-8621, Japan
2Department of Biomedical Laboratory Sciences, Shinshu University, Matsumoto 390-8621, Japan
3Institute of Advanced Biosciences, Keio University, Tsuruoka 997-0017, Japan

Received 11 March 2009; Revised 3 June 2009; Accepted 19 June 2009

Academic Editor: Changlin Li

Copyright © 2009 Kazuhiko Matsushita et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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 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.