ASC (apoptosis-associated speck-like protein containing a CARD), also known as TMS1 (target of methylation-induced silencing), was first identified in 1999 as a protein that forms aggregates, or specks, during retinoic acid-induced apoptosis in a human leukemia cell line (1). Furthermore, it was discovered to have a role as a tumor suppressor as methylation silences ASC/TMS1 expression in many tumors (2-5). ASC/TMS1 is synthesized as a 195-amino acid (aa) protein with a theoretical weight of 22 kDa. Structurally the protein contains a N-terminal PYD (pyrin domain) and C-terminal CARD (caspase-recruitment domain) (1-4). Historically, CARD and PYD-containing proteins are known to have crucial functions in regulating apoptosis and immune response pathways (2-5). Furthermore, mutations in many CARD and PYD-containing proteins have been linked to various cancers and inflammatory diseases (2-5). Given its immune response role, it is not surprising that ASC/TMS1 is typically highly expressed in immune cells, specifically in neutrophils and cells of the macrophage/monocyte lineage (5). Additionally, it is expressed in many normal epithelial cell types (4,5).
In regard to immune and inflammatory response, ASC/TMS1 is involved in inflammasome function (3-4). The inflammasome is a multiprotein complex that responds to cellular stress or pathogens and activates inflammatory responses. Specifically, ASC/TMS1 helps assemble the NLRP3 inflammasome complex which then activates caspase-1, followed by stimulation of proinflammatory cytokines including IL-1b and IL-18 (3-4). In terms of the role in regulating apoptosis, multiple studies have revealed that the ASC/TMS1 gene is hypermethylated in many cancers including breast, lung, glioblastomas, and melanomas (2-5). The increased methylation results in decreased gene expression, or silencing, allowing those cancer cells to escape apoptosis (2-5).
1. Masumoto, J., Taniguchi, S., Ayukawa, K., Sarvotham, H., Kishino, T., Niikawa, N., Hidaka, E., Katsuyama, T., Higuchi, T., & Sagara, J. (1999). ASC, a novel 22-kDa protein, aggregates during apoptosis of human promyelocytic leukemia HL-60 cells. The Journal of biological chemistry, 274(48), 33835-33838. https://doi.org/10.1074/jbc.274.48.33835
2. McConnell, B. B., & Vertino, P. M. (2004). TMS1/ASC: the cancer connection. Apoptosis: an international journal on programmed cell death. https://doi.org/10.1023/B:APPT.0000012117.32430.0c
3. Salminen, A., Kauppinen, A., Hiltunen, M., & Kaarniranta, K. (2014). Epigenetic regulation of ASC/TMS1 expression: potential role in apoptosis and inflammasome function. Cellular and molecular life sciences : CMLS. https://doi.org/10.1007/s00018-013-1524-9
4. Protti, M. P., & De Monte, L. (2020). Dual Role of Inflammasome Adaptor ASC in Cancer. Frontiers in cell and developmental biology. https://doi.org/10.3389/fcell.2020.00040
5. Parsons, M. J., & Vertino, P. M. (2006). Dual role of TMS1/ASC in death receptor signaling. Oncogene. https://doi.org/10.1038/sj.onc.1209684
|Product By Gene ID
- apoptosis-associated speck-like protein containing a CARD
- Target of methylation-induced silencing 1
- Caspase recruitment domain-containing protein 5
- caspase recruitment domain protein 5
- PYD and CARD domain-containing protein