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Journal of Virology, October 2000, p. 9680-9693, Vol. 74, No. 20
Department of Molecular Virology and
Microbiology, Baylor College of Medicine, Houston, Texas
77030,1 and International Center for
Genetic Engineering and Biotechnology, I-34012 Trieste,
Italy2
Received 10 April 2000/Accepted 13 July 2000
A general theme that has emerged from studies of DNA tumor viruses
is that otherwise unrelated oncoproteins encoded by these viruses often
target the same important cellular factors. Major oncogenic
determinants for human adenovirus type 9 (Ad9) and high-risk human
papillomaviruses (HPV) are the E4-ORF1 and E6 oncoproteins, respectively, and although otherwise unrelated, both of these viral
proteins possess a functional PDZ domain-binding motif that is
essential for their transforming activity and for binding to the PDZ
domain-containing and putative tumor suppressor protein DLG. We report
here that the PDZ domain-binding motifs of Ad9 E4-ORF1 and high-risk
HPV-18 E6 also mediate binding to the widely expressed cellular factor
MUPP1, a large multi-PDZ domain protein predicted to function as an
adapter in signal transduction. With regard to the consequences of
these interactions in cells, we showed that Ad9 E4-ORF1 aberrantly
sequesters MUPP1 within the cytoplasm of cells whereas HPV-18 E6
targets this cellular protein for degradation. These effects were
specific because mutant viral proteins unable to bind MUPP1 lack these
activities. From these results, we propose that the multi-PDZ domain
protein MUPP1 is involved in negatively regulating cellular
proliferation and that the transforming activities of two different
viral oncoproteins depend, in part, on their ability to inactivate this
cellular factor.
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Multi-PDZ Domain Protein MUPP1 Is a Cellular Target
for both Adenovirus E4-ORF1 and High-Risk Papillomavirus Type 18 E6 Oncoproteins
*
Corresponding author. Mailing address: Department of
Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: (713) 798-3898. Fax: (713) 798-3586. E-mail: rjavier{at}bcm.tmc.edu.
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