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Establishment of a Clinic-based Biorepository
Published on: May 29, 2017
Possible oncogenic potential of DeltaNp73: a newly identified isoform of human p73
Osamu Ishimoto1, Chikashi Kawahara, Kentaro Enjo
1Department of Cell Biology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Abstract:
p73, a recently identified gene highly homologous to p53, can transactivate p53 target genes and induce apoptosis. Here we report the identification of an NH(2)-terminal truncated isoform of human p73, DeltaNp73, which is capable of suppressing p53- and p73-dependent transactivation. We speculate that this suppression is achieved by competing for the DNA binding site in the case of p53 and by direct association in the case of TAp73. Expression of DeltaNp73 in cancer cell lines also inhibited suppressive activity of p53 and TAp73 in colony formation, implying possible involvement of DeltaNp73 in oncogenesis by inhibiting the tumor-suppressive function of p53 and TAp73. Also reported is the identification of TAp73eta, a new member of the COOH-terminal truncated isoform of p73 and tissue-specific expression of these isoforms, along with other previously identified p73 isoforms.
Insights
Researchers discovered DeltaNp73, a p73 gene isoform that suppresses the tumor-suppressive functions of p53 and p73. This finding suggests DeltaNp73 may play a role in oncogenesis by inhibiting these critical tumor suppressors.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- The p73 gene is homologous to p53 and plays a role in inducing apoptosis and transactivating p53 target genes.
- Understanding p73 isoforms is crucial for comprehending its role in cellular processes and disease.
Purpose of the Study:
- To identify and characterize novel isoforms of the human p73 gene.
- To investigate the functional impact of these isoforms on p53 and p73 activity.
- To explore the potential role of p73 isoforms in oncogenesis.
Main Methods:
- Identification of NH(2)-terminal truncated p73 isoform (DeltaNp73).
- Analysis of DeltaNp73's effect on p53- and p73-dependent transactivation.
- Assessment of DeltaNp73's impact on colony formation in cancer cell lines.
- Identification of a new COOH-terminal truncated p73 isoform (TAp73eta).
Main Results:
- DeltaNp73 was identified as an isoform capable of suppressing p53 and p73 transactivation.
- Suppression mechanisms likely involve competition for DNA binding (p53) and direct association (TAp73).
- DeltaNp73 inhibited the tumor-suppressive activities of p53 and TAp73 in colony formation assays.
- TAp73eta, a new COOH-terminal truncated isoform, was identified.
- Tissue-specific expression patterns of various p73 isoforms were reported.
Conclusions:
- DeltaNp73 acts as a functional antagonist to both p53 and TAp73.
- DeltaNp73 may contribute to oncogenesis by inhibiting tumor suppressor functions.
- The discovery of new p73 isoforms, including TAp73eta, expands our understanding of p73's complex role.
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