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Aberrant forms of the tumor suppressor protein p53 correlate with a
significant percentage of human cancer cell lines. In many cancers,
aberrant p53 correlates with highly aggressive tumor behavior, as
well as being an independent clinical prognostic marker of early
relapse and death. Delivery of active, functional p53 to cancer
cells shows promise as a potential cancer therapeutic strategy.
UCSD investigators have discovered a method of making the tumor
suppressor protein p53 constitutively active in vivo. In cellular
responses to various stresses, wild type p53 is activated through
post-translational modifications that change its conformation,
leading to cell cycle arrest and cellular apoptosis. While p53 is
critical for suppression of human cancers, delivery of a wt p53 into
cancer cells usually requires its activation in order to suppress
tumors. Many cancer cells do not have the required
post-translational mechanisms to activate p53, and therefore a
constitutively active p53 could be more useful as a therapeutic
agent. Its utility has been demonstrated in vivo in a transgenic
mouse model.
COMMERCIAL APPLICATIONS: A constitutively active p53 protein could be
utilized in a delivery system targeting therapeutic proteins (or the
corresponding DNA or RNA) to tumors. It could also be useful as a
drug screening target to overcome inhibitors or enhance activators of
the p53 activation pathway.
Case No: SD2004-160
Inquiries To: invent@ucsd.edu
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