- Research article
Acheron, an novel LA antigen family member, binds to cask and forms a complex with id transcription factors
Cellular & Molecular Biology Letters volume 14, pages 273–287 (2009)
Acheron, a Lupus antigen ortholog, was identified as a novel death-associated transcript from the intersegmental muscles of the mothManduca sexta. Acheron is phylogenetically-conserved and represents a new sub-family of Lupus antigen proteins. Acheron is expressed predominantly in neurons and muscle in vertebrates, and regulates several developmental events including myogenesis, neurogenesis and possibly metastasis. Using Acheron as bait, we performed a yeast two-hybrid screen with a mouse embryo cDNA library and identified CASK-C, a novel CASK/Lin-2 isoform, as an Acheron binding partner. Acheron and CASK-C bind via the C-terminus of Acheron and the CaMKII-like domain of CASK-C. Co-immunoprecipitation assays verify this interaction and demonstrate that Acheron also forms a complex with all members of the Id (inhibitor of differentiation) proteins. Taken together, these data suggest a mechanism by which Acheron may regulate development and pathology.
Ca2+/calmodulin-dependent serine protein kinase
glutathione S transferase
inhibitor of differentiation
Valavanis, C., Wang, Z., Sun, D., Vaine, M. and Schwartz, L.M. Acheron, a novel member of the Lupus antigen family, is induced during the programmed cell death of skeletal muscles in the moth Manduca sexta. Gene 393 (2007) 101–109.
Hata, Y., Butz, S., and Sudhof, T.C. CASK: a novel dlg/PSD95 homolog with an N-terminal calmodulin-dependent protein kinase domain identified by interaction with neurexins. J. Neurosci. 16 (1996) 2488–2494.
Dimitratos, S.D., Woods, D.F. and Bryant, P.J. Camguk, Lin-2, and CASK: novel membrane-associated guanylate kinase homologs that also contain CaM kinase domains. Mech. Dev. 63 (1997) 127–130.
Caruana, G. Genetic studies define MAGUK proteins as regulators of epithelial cell polarity. Int. J. Dev. Biol. 46 (2002) 511–518.
Atasoy, D., Schoch, S., Ho, A., Nadasy, K.A., Liu, X., Zhang, W., Mukherjee, K., Nosyreva, E.D., Fernandez-Chacon, R., Missler, N., Kavalali, E.T. and Sudhof, T.C. Deletion of CASK in mice is lethal and impairs synaptic function. Proc. Natl. Acad. Sci. USA 104 (2007) 2525–2530.
Boudeau, J., Miranda-Saavedra, D., Barton, G.J. and Alessi, D.R. Emerging roles of pseudokinases. Trends Cell Biol. 16 (2006) 443–452.
Hsueh, Y.P. The role of the MAGUK protein CASK in neural development and synaptic function. Curr. Med. Chem. 13 (2006) 1915–1927.
Hsueh, Y.P., Wang, T.F., Yang, F.C. and Sheng, M. Nuclear translocation and transcription regulation by the membrane-associated guanylate kinase CASK/LIN-2. Nature 404 (2000) 298–302.
Qi, J., Su, Y., Sun, R., Zhang, F., Luo, X., Yang, Z. and Luo, X. CASK inhibits ECV304 cell growth and interacts with Id1. Biochem. Biophys. Res. Commun. 328 (2005) 517–521.
Laverty, H.G. and Wilson, J.B. Murine CASK is disrupted in a sex-linked cleft palate mouse mutant. Genomics 53 (1998) 29–41.
Fallon, L., Moreau, F., Croft, B.G., Labib, N., Gu, W.J. and Fon, E.A. parkin and CASK/LIN-2 associate via a PDZ-mediated interaction and are co-localized in lipid rafts and postsynaptic densities in brain. J. Biol. Chem. 277 (2002) 486–491.
Fong, S., Debs, R.J. and Desprez, P.Y. Id genes and proteins as promising targets in cancer therapy. Trends Mol. Med. 10 (2004) 387–392.
Alfano, C., Sanfelice, D., Babon, J., Kelly, G., Jacks, A., Curry, S. and Conte, M.R. Structural analysis of cooperative RNA binding by the La motif and central RRM domain of human La protein. Nat. Struct. Mol. Biol. 11 (2004) 323–329.
Maraia, R.J. and Intine, R.V. La protein and its associated small nuclear and nucleolar precursor RNAs. Gene Expr. 10 (2002) 41–57.
Ohndorf, U.M., Steegborn, C., Knijff, R. and Sondermann, P. Contributions of the individual domains in human La protein to its RNA 3′-end binding activity. J. Biol. Chem. 276 (2001) 27188–27196.
Wolin, S.L. and Cedervall, T. The La protein. Annu. Rev. Biochem. 71 (2002) 375–403.
Park, J.M., Kohn, M.J., Bruinsma, M.W., Vech, C., Intine, R.V., Fuhrmann, S., Grinberg, A., Mukherjee, I., Love, P.E., Ko, M.S., DePamphilis, M.L. and Maraia, R.J. The multifunctional RNA-binding protein La is required for mouse development and for the establishment of embryonic stem cells. Mol. Cell Biol. 26 (2006) 1445–1451.
Ardley, H.C., Tan, N.G., Rose, S.A., Markham, A.F. and Robinson, P.A. Features of the parkin/ariadne-like ubiquitin ligase, HHARI, that regulates its interaction with the ubiquitin-conjugating enzyme, Ubch7. J. Biol. Chem. 276 (2001) 19640–19647.
Lehtonen, S., Lehtonen, E., Kudlicka, K., Holthofer, H. and Farquhar, M.G. Nephrin forms a complex with adherens junction proteins and CASK in podocytes and in Madin-Darby canine kidney cells expressing nephrin. Am. J. Pathol. 165 (2004) 923–936.
Sanford, J.L., Mays, T.A. and Rafael-Fortney, J.A. CASK and Dlg form a PDZ protein complex at the mammalian neuromuscular junction. Muscle Nerve 30 (2004) 164–171.
Schuh, K., Uldrijan, S., Gambaryan, S., Roethlein, S. and Neyses, L. Interaction of the plasma membrane Ca2+ pump 4b/CI with the Ca2+/calmodulin-dependent membrane-associated kinase CASK. J. Biol. Chem. 278 (2003) 9778–9783.
Lee, S., Fan, S., Makarova, O., Straight, S. and Margolis, B. A novel and conserved protein-protein interaction domain of mammalian Lin-2/CASK binds and recruits SAP97 to the lateral surface of epithelia. Mol. Cell Biol. 22 (2002) 1778–1791.
Martinez-Estrada, O.M., Villa, A., Breviario, F., Orsenigo, F., Dejana, E. and Bazzoni, G. Association of junctional adhesion molecule with calcium/calmodulin-dependent serine protein kinase (CASK/LIN-2) in human epithelial caco-2 cells. J. Biol. Chem. 276 (2001) 9291–9296.
Marble, D.D., Hegle, A.P., SnyderII, E.D., Dimitratos, S., Bryant, P.J. and Wilson, G.F. Camguk/CASK enhances Ether-á-go-go potassium current by a phosphorylation-dependent mechanism. J. Neurosci. 25 (2005) 4898–4907.
Leonoudakis, D., Conti, L.R., Radeke, C.M., McGuire, L.M. and Vandenberg, C.A. A multiprotein trafficking complex composed of SAP97, CASK, Veli, and Mint1 is associated with inward rectifier Kir2 potassium channels. J. Biol. Chem. 279 (2004) 19051–19063.
Maximov, A., Sudhof, T.C. and Bezprozvanny, I. Association of neuronal calcium channels with modular adaptor proteins. J. Biol. Chem. 274 (1999) 24453–24456.
Butz, S., Okamoto, M. and Sudhof, T.C. A tripartite protein complex with the potential to couple synaptic vesicle exocytosis to cell adhesion in brain. Cell 94 (1998) 773–782.
Tabuchi, K., Biederer, T., Butz, S., and Sudhof, T.C. CASK participates in alternative tripartite complexes in which Mint 1 competes for binding with caskin 1, a novel CASK-binding protein. J. Neurosci. 22 (2002) 4264–4273.
Yap, C.C., Liang, F., Yamazaki, T., Muto, Y., Kishida, H., Hayashida, T., Hashikawa, T. and Yano, R. CIP98, a novel PDZ domain protein, is expressed in the central nervous system and interacts with calmodulin-dependent serine kinase. J. Neurochem. 85 (2003) 123–134.
Cohen, A.R., Woods, D.F., Marfatia, S.M., Walther, Z., Chishti, A.H. and Anderson, J.M. Human CASK/LIN-2 binds syndecan-2 and protein 4.1 and localizes to the basolateral membrane of epithelial cells. J. Cell Biol. 142 (1998) 129–138.
Wang, G.S., Hong, C.J., Yen, T.Y., Huang, H.Y., Ou, Y., Huang T.N., Jung W.G., Kuo T.Y., Sheng, M., Wang, T.F. and Hsueh, Y.P. Transcriptional modification by a CASK-interacting nucleosome assembly protein. Neuron 42 (2004) 113–128.
An erratum to this article can be found at http://dx.doi.org/10.2478/s11658-009-0005-5
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Weng, H., Kim, C., Valavanis, C. et al. Acheron, an novel LA antigen family member, binds to cask and forms a complex with id transcription factors. Cell Mol Biol Lett 14, 273–287 (2009). https://doi.org/10.2478/s11658-008-0046-1
- Programmed cell death
- Manduca sexta
- Lupus antigen protein