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Mol Cell Biol, July 1998, p. 3735-3743, Vol. 18, No. 7
Department of Biochemistry, St. Jude
Children's Research Hospital, Memphis, Tennessee
38105,1 and
Department of
Biochemistry, University of Tennessee, Memphis, Tennessee
381632
Received 19 August 1997/Returned for modification 28 September
1997/Accepted 27 March 1998
Mutation of the p53 tumor suppressor gene is the most common
genetic alteration in human cancer, and tumors that express mutant p53
may be more aggressive and have a worse prognosis than p53-null cancers. Mutant p53 enhances tumorigenicity in the absence of a
transdominant negative mechanism, and this tumor-promoting activity correlates with its ability to transactivate reporter genes in transient transfection assays. However, the mechanism by which mutant
p53 functions in transactivation and its endogenous cellular targets
that promote tumorigenicity are unknown. Here we report that (i) mutant
p53 can regulate the expression of the endogenous c-myc
gene and is a potent activator of the c-myc promoter; (ii) the region of mutant p53 responsiveness in the c-myc gene
has been mapped to the 3' end of exon 1; (iii) the mutant p53 response region is position and orientation dependent and therefore does not
function as an enhancer; and (iv) transactivation by mutant p53
requires the C terminus, which is not essential for wild-type p53
transactivation. These data suggest that it may be possible to
selectively inhibit mutant p53 gain of function and consequently reduce
the tumorigenic potential of cancer cells. A possible mechanism for
transactivation of the c-myc gene by mutant p53 is
proposed.
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Activation of c-myc Gene Expression by
Tumor-Derived p53 Mutants Requires a Discrete C-Terminal
Domain

*
Corresponding author. Mailing address: Department of
Biochemistry, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105-2794. Phone: (901) 495-3429. Fax: (901)
525-8025. E-mail: gerard.zambetti{at}stjude.org.
Present address: Department of Clinical Chemistry, St. Jude
Children's Research Hospital, Memphis, TN 38105.
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