Dissecting the Functional Role of the TRIM8 Protein on Cancer Pathogenesis
Abstract
:Simple Summary
Abstract
1. Introduction
2. TRIM Proteins Biological Functions
- Degradation of toxic protein aggregates [39];
3. TRIM Proteins and Cancer Pathogenesis
- Chromosomal translocation [45]. It could generate a fusion protein without activity or with a different activity that could dysregulate some signaling pathways, leading to the generation of some tumor shapes. An example is a translocation between the TRIM19 gene (PML) on chromosome 15 and the retinoic acid receptor α (RARa) gene on chromosome 17. This translocation leads to the formation of a fusion protein that represses acid signaling retinoic and is associated with Acute Promyelocytic Leukemia [46]. Such similar examples are the following: TRIM24, TRIM27 and TRIM33 were found in translocations with the RET gene and are involved in papillary thyroid cancer, lymphoma and non-small cell lung carcinoma, respectively. Similarly, TRIM24 was found translocated with the BRAF gene in melanoma and lung cancer and with the FGFR1 gene in myeloproliferative syndrome [43];
- Modulation of the activity and stability of p53. TRIM11, TRIM13, TRIM21, TRIM24, TRIM25, TRIM28, TRIM29, TRIM31, TRIM32, TRIM39 and TRIM59 can ubiquitinate the p53 protein, a fundamental macromolecule in cell development whose purpose is to promote genomic stability and induce cell cycle arrest and apoptosis if extensive DNA damage is found in the cell. The ubiquitination of this protein leads to its direct degradation or to its sequestration in the cytoplasm: since it can no longer penetrate the nucleus, the ubiquitinated protein is no longer able to detect any damage to the DNA; consequently, the cell replicates itself by transmitting the same error in the nucleic acid sequence, resulting in the possible onset of tumor forms [47];
- Regulation of pathways to cancer stemness, including STAT signaling, AKT signaling, NANOGSox2-Oct-3/4 networks. Specifically, through these pathways, TRIM28 is involved in breast cancer, TRIM24 in glioblastoma and colorectal cancer, TRIMs 14 in gastric cancer and TRIM16 has been associated as a negative regulator of stemness in breast and ovarian cancer cells [43].
4. TRIM8
5. TRIM8 and Cancer Pathogenesis
6. TRIM8 as Tumor Suppressor
- By inducing the TP53 tumor suppressor activity through a positive feedback loop formation.
- Restoring TP53 functions by blunting N-MYC activity in chemo-resistant tumors.
- Quenching the DNp63a oncogenic activity by forming a negative feedback loop.
7. TRIM 8 as Oncogenic Protein
7.1. TRIM8 and NF-kB
7.2. TRIM8 and STAT3
8. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Esposito, J.E.; De Iuliis, V.; Avolio, F.; Liberatoscioli, E.; Pulcini, R.; Di Francesco, S.; Pennelli, A.; Martinotti, S.; Toniato, E. Dissecting the Functional Role of the TRIM8 Protein on Cancer Pathogenesis. Cancers 2022, 14, 2309. https://doi.org/10.3390/cancers14092309
Esposito JE, De Iuliis V, Avolio F, Liberatoscioli E, Pulcini R, Di Francesco S, Pennelli A, Martinotti S, Toniato E. Dissecting the Functional Role of the TRIM8 Protein on Cancer Pathogenesis. Cancers. 2022; 14(9):2309. https://doi.org/10.3390/cancers14092309
Chicago/Turabian StyleEsposito, Jessica Elisabetta, Vincenzo De Iuliis, Francesco Avolio, Eliana Liberatoscioli, Riccardo Pulcini, Simona Di Francesco, Alfonso Pennelli, Stefano Martinotti, and Elena Toniato. 2022. "Dissecting the Functional Role of the TRIM8 Protein on Cancer Pathogenesis" Cancers 14, no. 9: 2309. https://doi.org/10.3390/cancers14092309