Mumps virus small hydrophobic protein targets ataxin-1 ubiquitin-like interacting protein (ubiquilin 4)

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 (A1 Up) as a cellular target of the SH protein. A1 Up 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 A1 Up and demonstrates that a truncated protein fragment corresponding to aa 136-270 of A1 Up, 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 A1 Up leads to a redistribution of SH to punctate structures that co-localize with the 20S proteasome in transfected or infected mammalian cells.