Adenovirus RID complex enhances degradation of internalized tumour necrosis factor receptor 1 without affecting its rate of endocytosis.
The receptor internalization and degradation (RID) complex of adenovirus plays an important role in modulating the immune response by downregulating the surface levels of tumour necrosis factor receptor 1 (TNFR1), thereby inhibiting NF-kappaB activation. Total cellular content of TNFR1 is also reduced in the presence of RID, which can be inhibited by treatment with lysosomotropic agents. In this report, surface biotinylation experiments revealed that, although RID and TNFR1 were able to form a complex on the cell surface, the rate of TNFR1 endocytosis was not affected by RID. However, the degradation of internalized TNFR1 was enhanced significantly in the presence of RID. Therefore, these data suggest that RID downregulates TNFR1 levels by altering the fate of internalized TNFR1 that becomes associated with RID at the plasma membrane, probably by promoting its sorting into endosomal/lysosomal degradation compartments.
Chin
Y Rebecca
YR
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Forchheimer Building, Room 411, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Horwitz
Marshall S
MS
Division of Infectious Diseases, Department of Pediatrics, Albert Einstein College of Medicine, Forchheimer Building, Room 411, 1300 Morris Park Avenue, Bronx, NY 10461, USA.|Department of Microbiology and Immunology, Albert Einstein College of Medicine, Forchheimer Building, Room 411, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
D000256:Adenoviridae / Q000378:metabolism*; D017503:Adenovirus E3 Proteins / Q000502:physiology; D002460:Cell Line; D004705:Endocytosis; D006801:Humans; D046912:Multiprotein Complexes / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I; D053319:Tumor Necrosis Factor Decoy Receptors; D015854:Up-Regulation; D014764:Viral Proteins / Q000502:physiology*
D017503:Adenovirus E3 Proteins; D046912:Multiprotein Complexes; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D053319:Tumor Necrosis Factor Decoy Receptors; D014764:Viral Proteins; C069521:recombinant human tumor necrosis factor-binding protein-1