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).

References

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

Long Name

Apoptosis-Associated Speck-Like Protein Containing A CARD

Alternate Names

CARD5, PYCARD, TMS1

Gene Symbol

PYCARD

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Product Specific Notices for ASC/TMS1 Antibody (OTI3E9) [Alexa Fluor® 700]

Alexa Fluor (R) products are provided under an intellectual property license from Life Technologies Corporation. The purchase of this product conveys to the buyer the non-transferable right to use the purchased product and components of the product only in research conducted by the buyer (whether the buyer is an academic or for-profit entity). The sale of this product is expressly conditioned on the buyer not using the product or its components, or any materials made using the product or its components, in any activity to generate revenue, which may include, but is not limited to use of the product or its components: (i) in manufacturing; (ii) to provide a service, information, or data in return for payment; (iii) for therapeutic, diagnostic or prophylactic purposes; or (iv) for resale, regardless of whether they are resold for use in research. For information on purchasing a license to this product for purposes other than as described above, contact Life Technologies Corporation, 5791 Van Allen Way, Carlsbad, CA 92008 USA or outlicensing@lifetech.com. This conjugate is made on demand. Actual recovery may vary from the stated volume of this product. The volume will be greater than or equal to the unit size stated on the datasheet.

This product is for research use only and is not approved for use in humans or in clinical diagnosis. Primary Antibodies are guaranteed for 1 year from date of receipt.

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ASC/TMS1 Antibody (OTI3E9) [Alexa Fluor® 700]

Novus Biologicals, part of Bio-Techne | Catalog # NBP2-71853AF700

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Background: ASC