A recombinant cell-permeable p53 fusion protein is selectively stabilized under hypoxia and inhibits tumor cell growth.

Abstract:

:More than 50% of human tumors contain a mutation in p53. Over 90% of tumors are solid tumors. Solid tumors have low oxygenated regions, called hypoxic regions where the tumor cells are more resistant to radio- and chemo-therapy than their well-oxygenated counterparts. In this study, we constructed a cell-permeable p53 fusion protein with selective stability in the hypoxic region. The fusion protein contained the TAT peptide for transduction across membranes, the oxygen-dependent degradation domain of hypoxia-inducible factor-1alpha and wild-type p53. This protein was effectively delivered into tumor cells where it exerted anticancer activity leading to the inhibition of cancer cell growth in vitro and the reduction of tumor weight in vivo. Hence, the fusion protein can be a novel protein drug for antitumor therapies, especially for hypoxic tumor cells.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Yu Z,Wu J,Wu S,Jia P,Tong Y,Wu X,Wang Y

doi

10.1016/j.canlet.2009.01.030

subject

Has Abstract

pub_date

2009-06-28 00:00:00

pages

101-7

issue

1

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(09)00056-1

journal_volume

279

pub_type

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