In:
Journal of Virology, American Society for Microbiology, Vol. 77, No. 21 ( 2003-11), p. 11685-11696
Abstract:
Adenovirus (Ad) types 2 and 5 encode at least five proteins within the E3 transcription unit that help the virus evade the immune system. Two such proteins, RIDα (formerly E3-10.4K) and RIDβ (formerly E3-14.5K), form the RID (receptor internalization and degradation) complex (formerly E3-10.4K/14.5K). RID mediates clearance from the cell surface and lysosomal degradation of a number of important members in the tumor necrosis factor receptor (TNFR) superfamily and the receptor tyrosine kinase receptor family. Affected receptors include Fas, TRAIL (TNF-related apoptosis-inducing ligand) receptor 1 (TR1), TR2, and epidermal growth factor receptor (EGFR). Degradation of Fas and TRAIL receptors protects Ad-infected cells from apoptosis. To investigate the mechanism of action of RIDα, 14 mutant RIDα proteins, each containing a three- to five-amino-acid deletion, were constructed and then expressed from the E3 region of a replication-competent recombinant Ad in the same context as wild-type RIDα. Each mutant protein was characterized with regard to five physical properties associated with wild-type RIDα, namely, protein stability, proteolytic cleavage, insertion into the membrane, complex formation with RIDβ, and transport to the cell surface. Additionally, the mutant proteins were tested for their ability to mediate internalization and degradation of EGFR and Fas and to protect cells from Fas-mediated apoptosis. The majority of mutant RIDα proteins (8 out of 14) were physically similar to wild-type RIDα. With regard to functional characteristics, the cytoplasmic domain of RIDα is largely unimportant for receptor internalization and degradation and the extracellular domain of RIDα is important for down-regulation of EGFR but not Fas.
Type of Medium:
Online Resource
ISSN:
0022-538X
,
1098-5514
DOI:
10.1128/JVI.77.21.11685-11696.2003
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2003
detail.hit.zdb_id:
1495529-5
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