A novel approach to cancer treatment using structural hybrids of the p53 gene family View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2012-09-07

AUTHORS

Y Sasaki, Y Oshima, R Koyama, M Tamura, L Kashima, M Idogawa, T Yamashita, M Toyota, K Imai, Y Shinomura, T Tokino

ABSTRACT

The p53 tumor suppressor belongs to a gene family that includes two other structurally and functionally related members: p73 and p63. The regulation of p53 activity differs significantly from that of p73 and p63. To enhance the tumor suppressive activity of p53, we constructed six recombinant adenoviruses that encode hybrid proteins with three functional domains derived from either p53 or TAp63γ. The potency of these hybrid molecules in suppressing tumorigenesis was evaluated using in vitro and in vivo models. Of the hybrid molecules tested, one hybrid named p63–53O was the most potent activator of apoptosis in human cancer cells. The p63–53O hybrid is composed of the transcriptional activation domain and DNA-binding domain of TAp63γ and the oligomerization domain of p53. The p63–53O hybrid efficiently transactivated p53AIP1. Moreover, silencing of p53AIP1 partially abolished the apoptotic response to p63–53O in human cancer cells. The p53–p63 hybrid molecule is a novel potent anti-proliferative agent for the treatment of cancer. More... »

PAGES

749-756

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/cgt.2012.51

DOI

http://dx.doi.org/10.1038/cgt.2012.51

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1050688398

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22956039


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43 schema:description The p53 tumor suppressor belongs to a gene family that includes two other structurally and functionally related members: p73 and p63. The regulation of p53 activity differs significantly from that of p73 and p63. To enhance the tumor suppressive activity of p53, we constructed six recombinant adenoviruses that encode hybrid proteins with three functional domains derived from either p53 or TAp63γ. The potency of these hybrid molecules in suppressing tumorigenesis was evaluated using in vitro and in vivo models. Of the hybrid molecules tested, one hybrid named p63–53O was the most potent activator of apoptosis in human cancer cells. The p63–53O hybrid is composed of the transcriptional activation domain and DNA-binding domain of TAp63γ and the oligomerization domain of p53. The p63–53O hybrid efficiently transactivated p53AIP1. Moreover, silencing of p53AIP1 partially abolished the apoptotic response to p63–53O in human cancer cells. The p53–p63 hybrid molecule is a novel potent anti-proliferative agent for the treatment of cancer.
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