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Updated: May 12, 2026
Multiomics Analysis of TMEM200A as a Pan-Cancer Biomarker
Published on: September 15, 2023
Functions, divergence and clinical value of TAp73 isoforms in cancer
Stella Logotheti1, Athanasia Pavlopoulou, Sotiris Galtsidis
1Unit of Biomedical Applications, Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 48 Vas. Constantinou Ave, 11635, Athens, Greece.
Abstract:
The p73 gene encodes the tumour suppressive full-length TAp73 and N-terminal-truncated DNp73 isoforms that act as dominant negative inhibitors of TAp73. The overall effect of p73 in oncogenesis is thought to depend on the TAp73 to DNp73 isoforms' ratio. TAp73 isoforms include a number of C-terminal variants as a result of alternative splicing in 3'-end. TAp73 isoforms protect cells from oncogenic alterations in a multifaceted way since they are implicated in the suppression of all demonstrated hallmarks and enabling characteristics of cancer. Their best established role is in apoptosis, a process which seems to be differently affected by each TAp73 C-terminal variant. Based on previous findings and our thorough bioinformatics analysis, we highlight that TAp73 variants are functionally non-equivalent, since they present major differences in their transactivation efficiencies, protein interactions, response to DNA damage and apoptotic effects that are attributable to the primary structure of their C terminus. In this review, we summarise these differences and we unveil the link between crucial C-terminal motifs/residues and the oncosuppressive potential of TAp73 isoforms, emphasising on the importance of considering C terminus during the development of p73-based anticancer biologics.
Insights
The p73 gene
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- The p73 gene produces tumor-suppressive TAp73 and inhibitory DNp73 isoforms.
- The balance between TAp73 and DNp73 is crucial for controlling oncogenesis.
- TAp73 isoforms, generated by alternative splicing, have diverse roles in cancer suppression.
Purpose of the Study:
- To review the functional differences among TAp73 C-terminal variants.
- To elucidate the link between C-terminal structure and TAp73's oncosuppressive activity.
- To highlight the significance of the C terminus in developing p73-based cancer therapies.
Main Methods:
- Bioinformatics analysis of TAp73 variants.
- Review of existing literature on p73 function.
- Analysis of TAp73 isoform differences in transactivation, protein interactions, and DNA damage response.
Main Results:
- TAp73 C-terminal variants are functionally non-equivalent.
- Differences in transactivation efficiency, protein interactions, and apoptotic effects were observed.
- Specific C-terminal motifs/residues correlate with the oncosuppressive potential of TAp73 isoforms.
Conclusions:
- The C terminus critically dictates TAp73 isoform function and oncosuppressive activity.
- Understanding these C-terminal variations is vital for p73-targeted cancer biologics.
- Future cancer therapies should consider the specific TAp73 C-terminal variants for efficacy.
