A synthetic peptide corresponding to amino acids 83-102 (GQLQAATHQGSGAAPAGIQA) of human ASC/TMS1 was used as immunogen; GenBank no. NP_037390.2, which is also referred to as ASC/TMS1 isoform a. Isoform a is a 195 amino acid protein. Amino acids 85-102 of the peptide immunogen immunogen are 100% consevered in ASC/TMS1 isoform c, GenBank no. NP_660184.1. Isoform c is a 135 amino acid protein.
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TMS1apoptosis-associated speck-like protein containing a CARD
ASC [apoptosis-associated speck-like protein containing a CARD (caspase-recruitment domain)] is a bimodel protein containing a pyrin/paad domain (PYD/PAAD) and a caspase recruitment domain (CARD) (reviewed in McConnell and Vertino, 2004). ASC is also known as TMS1 (target of methylation-induced silencing). ASC was first identified in 1999 as a protein that forms cytoplasmic specks during retinoic acid induced differentiation or drug-induced apoptosis in HL60 cells. It was later independently identified in 2000 in a screen for targets of methylation-mediated silencing. In general proteins, like ASC/TMS1, containing PYD/PAAD and CARD domains play key roles in regulating apoptosis and inflammation signaling pathways. Mutations in a number of PYD/PAAD- and CARD-containing proteins have been linked to inflammatory diseases and cancer. There is evidence that ASC/TMS1 has roles in both apoptosis and inflammation signaling pathways. For example, ASC/TMS1 has been reported to function as a proapoptotic protein and has been shown to trigger apoptosis upon over expression in tumor cell lines. With respect to inflammation, ASC/TMS1 interacts with the CARD of procaspase-1 and induces aggregation of a protein complex called the inflammasome, thereby regulating caspase-1 activation and secretion of IL-1b. Additionally, ASC/TMS1 has been found to be subjected to methylation-mediated silencing in a significant proportion of human breast tumors and other cancers, including melanomas, glioblastomas, non-small lung cancers, gastric and colorectal cancers (reviewed in Parsons and Vertino, 2006). The loss of ASC/TMS1 expression in breast tumors and other cancers through methylation-mediated (epigenetic) silencing suggests that ASC/TMS1 has a role in tumorigenesis. In general, it is thought that methylation-mediated gene silencing contributes to tumorigenesis by inactivating genes involved in tumor suppression, and by conferring resistance to cell death signals by silencing genes that promote apoptosis. Thus methylation-mediated silencing of ASC/TMS1 may confer a survival advantage to tumor cells by enabling them to escape apoptosis. However, the precise role of ASC/TMS1 in the pathogenesis of cancer remains to be fully elucidated. Human ASC/TMS1 (isoform a) is a 195 amino acid protein (approx. 22 kDa), GenBank no. NP_037390.2. Three transcript variants encoding different isoforms have been identified for the ASC/TMS1 gene; please refer to AceView of NCBI (http://www.ncbi.nih.gov/IEB/Research/Acembly/) for detailed information. ASC/TMS1 is normally highly expressed in immune cells, especially in neutrophils and cells of the macrophage/monocyte lineage; it is also expressed in many epithelial cell types (reviewed in Parsons and Vertino, 2006).
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