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Journal of Virology, December 2000, p. 11407-11412, Vol. 74, No. 23
Laboratory of Genetics, The Salk Institute
for Biological Studies, La Jolla, California 92037
Received 11 April 2000/Accepted 12 September 2000
In adenovirus-infected cells, binding of E1B-55kDa and E4orf6 to
the tumor suppressor protein p53 inhibits its transcriptional activity
and causes rapid turnover of the protein. To investigate the
requirements of the E1B-E4orf6 complex to modulate p53 function, we
generated an E4orf6 mutant that failed to associate functionally and
physically with E1B-55kDa but still interacted with p53. We confirm
that E4orf6 and E1B-55kDa reduce p53 transactivation individually and
show that their combined inhibition is additive rather than synergistic. Furthermore, we found that downregulation of p53's expression level, but not transcriptional inhibition of p53, depends on
a functional E1B-E4 complex. A functional interaction of E1B-55kDa with
p53, on the other hand, is a prerequisite for both transcriptional repression and downregulation of p53. The separation of these two
functions will enable further dissection of the requirements for
oncogenicity by the E4orf6 protein.
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
A Functional Complex of Adenovirus Proteins
E1B-55kDa and E4orf6 Is Necessary To Modulate the Expression Level of
p53 but Not Its Transcriptional Activity
*
Corresponding author. Mailing address: Laboratory of
Genetics, The Salk Institute, 10010 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 453-4100, ext. 2037. Fax: (858) 558-7454. E-mail: weitzman{at}salk.edu.
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