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J Biol Chem. 2002 Apr 19;277(16):14177-85. Epub 2002 Feb 13.

Transactivation-deficient Delta TA-p73 inhibits p53 by direct competition for DNA binding: implications for tumorigenesis.

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  • 1Centre for Cancer Research and Cancer Therapy, Institute of Molecular Biology, University of Essen, Medical School, D-45122 Essen, Germany.


The p53 family member p73 displays significant structural and functional homology to p53. However, instead of mutational inactivation, overexpression of wild-type p73 has been reported in various tumor types compared with normal tissues, arguing against a classical tumor suppressor function. Recently, N-terminally truncated, transactivation-deficient p73 isoforms (DeltaTA-p73) have been identified as a second class of p73 proteins. Because overexpression of p73 in tumors includes DeltaTA-p73, we further characterized these novel p73 isoforms. We show that DeltaTA-p73 retains DNA-binding competence but lacks transactivation functions, resulting in an inability to induce growth arrest and apoptosis. Importantly, DeltaTA-p73 acts as a dominant-negative inhibitor of p53 and full-length p73 (TA-p73). We demonstrate that inhibition of p53 involves competition for DNA binding, whereas TA-p73 can be inhibited by direct protein-protein interaction. Further, we show that up-regulation of endogenous p73 just like ectopic overexpression of DeltaTA-p73 confers resistance to p53-mediated apoptosis induced by the chemotherapeutic agent H-7. Because inhibition of p53 is a common theme in human cancer, our data strongly support a role of DeltaTA-p73 expression for tumor formation.

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