PYCARD
Apoptosis-associated speck-like protein containing a CARD or ASC is a protein that in humans is encoded by the PYCARD gene.[1]
This gene encodes an adaptor protein that is composed of two protein–protein interaction domains: a N-terminal PYRIN-PAAD-DAPIN domain (PYD) and a C-terminal caspase-recruitment domain (CARD). The PYD and CARD domains are members of the six-helix bundle death domain-fold superfamily that mediates assembly of large signaling complexes in the inflammatory and apoptotic signaling pathways via the activation of caspase. In normal cells, this protein is localized to the cytoplasm; however, in cells undergoing apoptosis, it forms ball-like aggregates near the nuclear periphery. Two transcript variants encoding different isoforms have been found for this gene.[1]
Interactions
PYCARD has been shown to interact with MEFV.[2]
References
Further reading
- Masumoto J, Taniguchi S, Ayukawa K, et al. (1999). "ASC, a novel 22-kDa protein, aggregates during apoptosis of human promyelocytic leukemia HL-60 cells.". J. Biol. Chem. 274 (48): 33835–8. doi:10.1074/jbc.274.48.33835. PMID 10567338.
- Lee SK, Na SY, Jung SY, et al. (2000). "Activating protein-1, nuclear factor-kappaB, and serum response factor as novel target molecules of the cancer-amplified transcription coactivator ASC-2.". Mol. Endocrinol. 14 (6): 915–25. doi:10.1210/me.14.6.915. PMID 10847592.
- Conway KE, McConnell BB, Bowring CE, et al. (2000). "TMS1, a novel proapoptotic caspase recruitment domain protein, is a target of methylation-induced gene silencing in human breast cancers.". Cancer Res. 60 (22): 6236–42. PMID 11103776.
- McConnell BB, Vertino PM (2000). "Activation of a caspase-9-mediated apoptotic pathway by subcellular redistribution of the novel caspase recruitment domain protein TMS1.". Cancer Res. 60 (22): 6243–7. PMID 11103777.
- Martinon F, Hofmann K, Tschopp J (2001). "The pyrin domain: a possible member of the death domain-fold family implicated in apoptosis and inflammation.". Curr. Biol. 11 (4): R118–20. doi:10.1016/S0960-9822(01)00056-2. PMID 11250163.
- Geddes BJ, Wang L, Huang WJ, et al. (2001). "Human CARD12 is a novel CED4/Apaf-1 family member that induces apoptosis.". Biochem. Biophys. Res. Commun. 284 (1): 77–82. doi:10.1006/bbrc.2001.4928. PMID 11374873.
- Richards N, Schaner P, Diaz A, et al. (2001). "Interaction between pyrin and the apoptotic speck protein (ASC) modulates ASC-induced apoptosis.". J. Biol. Chem. 276 (42): 39320–9. doi:10.1074/jbc.M104730200. PMID 11498534.
- Stimson KM, Vertino PM (2002). "Methylation-mediated silencing of TMS1/ASC is accompanied by histone hypoacetylation and CpG island-localized changes in chromatin architecture.". J. Biol. Chem. 277 (7): 4951–8. doi:10.1074/jbc.M109809200. PMID 11733524.
- Manji GA, Wang L, Geddes BJ, et al. (2002). "PYPAF1, a PYRIN-containing Apaf1-like protein that assembles with ASC and regulates activation of NF-kappa B.". J. Biol. Chem. 277 (13): 11570–5. doi:10.1074/jbc.M112208200. PMID 11786556.
- Srinivasula SM, Poyet JL, Razmara M, et al. (2002). "The PYRIN-CARD protein ASC is an activating adaptor for caspase-1.". J. Biol. Chem. 277 (24): 21119–22. doi:10.1074/jbc.C200179200. PMID 11967258.
- Wang L, Manji GA, Grenier JM, et al. (2002). "PYPAF7, a novel PYRIN-containing Apaf1-like protein that regulates activation of NF-kappa B and caspase-1-dependent cytokine processing.". J. Biol. Chem. 277 (33): 29874–80. doi:10.1074/jbc.M203915200. PMID 12019269.
- Shiohara M, Taniguchi S, Masumoto J, et al. (2002). "ASC, which is composed of a PYD and a CARD, is up-regulated by inflammation and apoptosis in human neutrophils.". Biochem. Biophys. Res. Commun. 293 (5): 1314–8. doi:10.1016/S0006-291X(02)00384-4. PMID 12054656.
- Martinon F, Burns K, Tschopp J (2002). "The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta.". Mol. Cell 10 (2): 417–26. doi:10.1016/S1097-2765(02)00599-3. PMID 12191486.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
- Stehlik C, Fiorentino L, Dorfleutner A, et al. (2003). "The PAAD/PYRIN-family protein ASC is a dual regulator of a conserved step in nuclear factor kappaB activation pathways.". J. Exp. Med. 196 (12): 1605–15. doi:10.1084/jem.20021552. PMC 2196065. PMID 12486103. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2196065.
- Moriai R, Tsuji N, Kobayashi D, et al. (2003). "A proapoptotic caspase recruitment domain protein gene, TMS1, is hypermethylated in human breast and gastric cancers.". Anticancer Res. 22 (6C): 4163–8. PMID 12553049.
- Dowds TA, Masumoto J, Chen FF, et al. (2003). "Regulation of cryopyrin/Pypaf1 signaling by pyrin, the familial Mediterranean fever gene product.". Biochem. Biophys. Res. Commun. 302 (3): 575–80. doi:10.1016/S0006-291X(03)00221-3. PMID 12615073.
- Masumoto J, Dowds TA, Schaner P, et al. (2003). "ASC is an activating adaptor for NF-kappa B and caspase-8-dependent apoptosis.". Biochem. Biophys. Res. Commun. 303 (1): 69–73. doi:10.1016/S0006-291X(03)00309-7. PMID 12646168.
- Stehlik C, Krajewska M, Welsh K, et al. (2003). "The PAAD/PYRIN-only protein POP1/ASC2 is a modulator of ASC-mediated nuclear-factor-kappa B and pro-caspase-1 regulation.". Biochem. J. 373 (Pt 1): 101–13. doi:10.1042/BJ20030304. PMC 1223462. PMID 12656673. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1223462.
- Levine JJ, Stimson-Crider KM, Vertino PM (2003). "Effects of methylation on expression of TMS1/ASC in human breast cancer cells.". Oncogene 22 (22): 3475–88. doi:10.1038/sj.onc.1206430. PMID 12776200.
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PDB gallery
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1ucp: NMR structure of the PYRIN domain of human ASC
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