The small hydrophobic (SH) protein of mumps virus has been reported to interfere with innate immunity by inhibiting tumour necrosis factor alpha-mediated apoptosis. In a yeast two-hybrid screen we have identified the ataxin-1 ubiquitin-like interacting protein (A1Up) as a cellular target of the SH protein. A1Up contains an amino-terminal ubiquitin-like (UbL) domain, a carboxy-terminal ubiquitin-associated (UbA) domain and two stress-inducible heat shock chaperonin-binding (Sti1) motifs. This places it within the ubiquitin-like protein family that is involved in proteasome-mediated activities. Co-immunoprecipitation confirmed the binding of SH and A1Up and demonstrates that a truncated protein fragment corresponding to aa 136–270 of A1Up, which represents the first Sti1-like repeat and an adjacent hydrophobic region, was sufficient for interaction, whereas neither the UbL nor the UbA domains were required for interaction. The ectopic expression of A1Up leads to a redistribution of SH to punctate structures that co-localize with the 20S proteasome in transfected or infected mammalian cells.


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  1. Afzal, M. A., Elliott, G. D., Rima, B. K. & Orvell, C.(1990). Virus and host cell-dependent variation in transcription of the mumps virus genome. J Gen Virol 71, 615–619.[CrossRef] [Google Scholar]
  2. Afzal, M. A., Pickford, A. R., Forsey, T., Heath, A. B. & Minor, P. D.(1993). The Jeryl Lynn vaccine strain of mumps virus is a mixture of two distinct isolates. J Gen Virol 74, 917–920.[CrossRef] [Google Scholar]
  3. Arya, R., Mallik, M. & Lakhotia, S. C.(2007). Heat shock genes – integrating cell survival and death. J Biosci 32, 595–610.[CrossRef] [Google Scholar]
  4. Campanella, M., de Jong, A. S., Lanke, K. W., Melchers, W. J., Willems, P. H., Pinton, P., Rizzuto, R. & van Kuppeveld, F. J.(2004). The coxsackievirus 2B protein suppresses apoptotic host cell responses by manipulating intracellular Ca2+ homeostasis. J Biol Chem 279, 18440–18450.[CrossRef] [Google Scholar]
  5. Carbone, K. & Rubin, S. A.(2007).Paramyxoviridae: mumps virus. In Fields Virology, 5th edn, pp. 1527–1550. Edited by Knipe., D. M. & Howley., P. M. Baltimore, MD. : Williams & Wilkins. [Google Scholar]
  6. Davidson, J. D., Riley, B., Burright, E. N., Duvick, L. A., Zoghbi, H. Y. & Orr, H. T.(2000). Identification and characterization of an ataxin-1-interacting protein: A1Up, a ubiquitin-like nuclear protein. Hum Mol Genet 9, 2305–2312.[CrossRef] [Google Scholar]
  7. Feng, P., Park, J., Lee, B. S., Lee, S. H., Bram, R. J. & Jung, J. U.(2002). Kaposi's sarcoma-associated herpesvirus mitochondrial K7 protein targets a cellular calcium-modulating cyclophilin ligand to modulate intracellular calcium concentration and inhibit apoptosis. J Virol 76, 11491–11504.[CrossRef] [Google Scholar]
  8. Feng, P., Scott, C. W., Cho, N. H., Nakamura, H., Chung, Y. H., Monteiro, M. J. & Jung, J. U.(2004). Kaposi's sarcoma-associated herpesvirus K7 protein targets a ubiquitin-like/ubiquitin-associated domain-containing protein to promote protein degradation. Mol Cell Biol 24, 3938–3948.[CrossRef] [Google Scholar]
  9. Ford, D. L. & Monteiro, M. J.(2006). Dimerization of ubiquilin is dependent upon the central region of the protein: evidence that the monomer, but not the dimer, is involved in binding presenilins. Biochem J 399, 397–404.[CrossRef] [Google Scholar]
  10. Fuentes, S., Tran, K. C., Luthra, P., Teng, M. N. & He, B.(2007). Function of the respiratory syncytial virus small hydrophobic protein. J Virol 81, 8361–8366.[CrossRef] [Google Scholar]
  11. Gonzalez, M. E. & Carrasco, L.(2003). Viroporins. FEBS Lett 552, 28–34.[CrossRef] [Google Scholar]
  12. Hiyama, H., Yokoi, M., Masutani, C., Sugasawa, K., Maekawa, T., Tanaka, K., Hoeijmakers, J. H. & Hanaoka, F.(1999). Interaction of hHR23 with S5a. The ubiquitin-like domain of hHR23 mediates interaction with S5a subunit of 26 S proteasome. J Biol Chem 274, 28019–28025.[CrossRef] [Google Scholar]
  13. Jin, L., Rima, B., Brown, D., Orvell, C., Tecle, T., Afzal, M., Uchida, K., Nakayama, T., Song, J. W. & other authors(2005). Proposal for genetic characterisation of wild-type mumps strains: preliminary standardisation of the nomenclature. Arch Virol 150, 1903–1909.[CrossRef] [Google Scholar]
  14. Kaye, F. J., Modi, S., Ivanovska, I., Koonin, E. V., Thress, K., Kubo, A., Kornbluth, S. & Rose, M. D.(2000). A family of ubiquitin-like proteins binds the ATPase domain of Hsp70-like Stch. FEBS Lett 467, 348–355.[CrossRef] [Google Scholar]
  15. Kochva, U., Leonov, H. & Arkin, I. T.(2003). Modeling the structure of the respiratory syncytial virus small hydrophobic protein by silent-mutation analysis of global searching molecular dynamics. Protein Sci 12, 2668–2674.[CrossRef] [Google Scholar]
  16. Lemon, K., Rima, B. K., McQuaid, S., Allen, I. V. & Duprex, W. P.(2007). The F gene of rodent brain-adapted mumps virus is a major determinant of neurovirulence. J Virol 81, 8293–8302.[CrossRef] [Google Scholar]
  17. Matsuda, M., Koide, T., Yorihuzi, T., Hosokawa, N. & Nagata, K.(2001). Molecular cloning of a novel ubiquitin-like protein, UBIN, that binds to ER targeting signal sequences. Biochem Biophys Res Commun 280, 535–540.[CrossRef] [Google Scholar]
  18. Nagata, K.(1996). Hsp47: a collagen-specific molecular chaperone. Trends Biochem Sci 21, 22–26. [Google Scholar]
  19. Perez, M., Garcia-Barreno, B., Melero, J. A., Carrasco, L. & Guinea, R.(1997). Membrane permeability changes induced in Escherichia coli by the SH protein of human respiratory syncytial virus. Virology 235, 342–351.[CrossRef] [Google Scholar]
  20. Riley, B. E., Xu, Y., Zoghbi, H. Y. & Orr, H. T.(2004). The effects of the polyglutamine repeat protein ataxin-1 on the UbL-UBA protein A1Up. J Biol Chem 279, 42290–42301.[CrossRef] [Google Scholar]
  21. Rubin, S. A., Amexis, G., Pletnikov, M., Li, Z., Vanderzanden, J., Mauldin, J., Sauder, C., Malik, T., Chumakov, K. & Carbone, K. M.(2003). Changes in mumps virus gene sequence associated with variability in neurovirulent phenotype. J Virol 77, 11616–11624.[CrossRef] [Google Scholar]
  22. Sambrook, J. & Russell, D. W.(2001).Molecular Cloning: a Laboratory Manual. Cold Spring Harbor, NY. : Cold Spring Harbor Laboratory. [Google Scholar]
  23. Santos, C. L., Ishida, M. A., Foster, P. G., Sallum, M. A., Benega, M. A., Borges, D. B., Correa, K. O., Constantino, C. R., Afzal, M. A. & Paiva, T. M.(2008). Detection of a new mumps virus genotype during parotitis epidemic of 2006–2007 in the state of Sao Paulo, Brazil. J Med Virol 80, 323–329.[CrossRef] [Google Scholar]
  24. Takayama, S., Bimston, D. N., Matsuzawa, S., Freeman, B. C., Aime-Sempe, C., Xie, Z., Morimoto, R. I. & Reed, J. C.(1997). BAG-1 modulates the chaperone activity of Hsp70/Hsc70. EMBO J 16, 4887–4896.[CrossRef] [Google Scholar]
  25. Takeuchi, K., Tanabayashi, K., Hishiyama, M., Yamada, A. & Sugiura, A.(1991). Variations of nucleotide sequences and transcription of the SH gene among mumps virus strains. Virology 181, 364–366.[CrossRef] [Google Scholar]
  26. Takeuchi, K., Tanabayashi, K., Hishiyama, M. & Yamada, A.(1996). The mumps virus SH protein is a membrane protein and not essential for virus growth. Virology 225, 156–162.[CrossRef] [Google Scholar]
  27. Wang, H. W., Sharp, T. V., Koumi, A., Koentges, G. & Boshoff, C.(2002). Characterization of an anti-apoptotic glycoprotein encoded by Kaposi's sarcoma-associated herpesvirus which resembles a spliced variant of human survivin. EMBO J 21, 2602–2615.[CrossRef] [Google Scholar]
  28. Watson, J. C., Hadler, S. C., Dykewicz, C. A., Reef, S. & Phillips, L.(1998). Measles, mumps, and rubella – vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 47 (RR-8), 1–57. [Google Scholar]
  29. Wilson, R. L., Fuentes, S. M., Wang, P., Taddeo, E. C., Klatt, A., Henderson, A. J. & He, B.(2006). Function of small hydrophobic proteins of paramyxovirus. J Virol 80, 1700–1709.[CrossRef] [Google Scholar]
  30. Yates, P. J., Afzal, M. A. & Minor, P. D.(1996). Antigenic and genetic variation of the HN protein of mumps virus strains. J Gen Virol 77, 2491–2497.[CrossRef] [Google Scholar]

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vol. , part 11, pp. 2773 –2781

Sequences of primers.

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