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 (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&emsp14;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.
Woznik
Maria
M
Department of Biology, Chemistry and Pharmacy, FU-Berlin, Berlin, Germany.
Rödner
Claudia
C
Lemon
Ken
K
Rima
Bert
B
Mankertz
Annette
A
Finsterbusch
Tim
T
D020816:Amino Acid Motifs; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D054884:Host-Pathogen Interactions; D006801:Humans; D047468:Immunoprecipitation; D018613:Microscopy, Confocal; D009109:Mumps virus / Q000472:pathogenicity*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D020798:Two-Hybrid System Techniques; D014764:Viral Proteins / Q000378:metabolism*
D002352:Carrier Proteins; D009687:Nuclear Proteins; C421907:UBQLN4 protein, human; D014764:Viral Proteins; C067386:small hydrophobic protein, Mumps virus