Affiliation:
1. Molecular Biology Institute, Department of Microbiology, Immunology and Molecular
Genetics, University of California, Los Angeles, California
Abstract
ABSTRACT
Theadenovirus type 5 (Ad5) E1B-55K and E4orf6 proteins are required
together to stimulate viral late nuclear mRNA export to the cytoplasm
and to restrict host cell nuclear mRNA export during the late phase of
infection. Previous studies have shown that these two viral proteins
interact with the cellular proteins elongins B and C,
cullin 5, RBX1, and additional cellular proteins to form an E3
ubiquitin-protein ligase that polyubiquitinates p53 and probably one or
more subunits of the MRE11-RAD50-NBS1 (MRN) complex, directing their
proteasomal degradation. The MRN complex is required for cellular DNA
double-strand break repair and induction of the DNA damage response by
adenovirus infection. To determine if the ability of E1B-55K and E4orf6
to stimulate viral late mRNA nuclear export requires the
ubiquitin-protein ligase activity of this viral ubiquitin-protein
ligase complex, we designed and expressed a dominant-negative mutant
form of cullin 5 in HeLa cells before infection with wild-type Ad5 or
the E1B-55K null mutant
dl
1520. The dominant-negative cullin 5
protein stabilized p53 and the MRN complex, indicating that it
inhibited the viral ubiquitin-protein ligase but had no effect on viral
early mRNA synthesis, early protein synthesis, or viral DNA
replication. However, expression of the dominant-negative cullin 5
protein caused a decrease in viral late protein synthesis and viral
nuclear mRNA export similar to the phenotype produced by mutations in
E1B-55K. We conclude that the stimulation of adenovirus late mRNA
nuclear export by E1B-55K and E4orf6 results from the ubiquitin-protein
ligase activity of the adenovirus ubiquitin-protein ligase
complex.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
Cited by
76 articles.
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