TRIM25, TRIM28 and TRIM59 and Their Protein Partners in Cancer Signaling Crosstalk: Potential Novel Therapeutic
De Chen Chiang1, Beow Keat Yap1
1School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor, Penang 11800, Malaysia.
Abstract:
Aberrant expression of TRIM proteins has been correlated with poor prognosis and metastasis in many cancers, with many TRIM proteins acting as key oncogenic factors. TRIM proteins are actively involved in many cancer signaling pathways, such as p53, Akt, NF-κB, MAPK, TGFβ, JAK/STAT, AMPK and Wnt/β-catenin. Therefore, this review attempts to summarize how three of the most studied TRIMs in recent years (i.e., TRIM25, TRIM28 and TRIM59) are involved directly and indirectly in the crosstalk between the signaling pathways. A brief overview of the key signaling pathways involved and their general cross talking is discussed. In addition, the direct interacting protein partners of these TRIM proteins are also highlighted in this review to give a picture of the potential protein-protein interaction that can be targeted for future discovery and for the development of novel therapeutics against cancer. This includes some examples of protein partners which have been proposed to be master switches to various cancer signaling pathways.
Insights
Aberrant expression of tripartite motif (TRIM) proteins drives cancer progression. This review details how TRIM25, TRIM28, and TRIM59 proteins interact with key cancer signaling pathways, offering therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Aberrant expression of tripartite motif (TRIM) proteins is linked to poor cancer prognosis and metastasis.
- TRIM proteins are integral to numerous cancer-associated signaling pathways, including p53, Akt, NF-κB, MAPK, TGFβ, JAK/STAT, AMPK, and Wnt/β-catenin.
Purpose of the Study:
- To review the direct and indirect roles of TRIM25, TRIM28, and TRIM59 in the crosstalk between cancer signaling pathways.
- To highlight protein-protein interactions involving these TRIM proteins as potential therapeutic targets.
Main Methods:
- Literature review of studies focusing on TRIM proteins and their involvement in cancer signaling pathways.
- Analysis of direct protein-interacting partners of TRIM25, TRIM28, and TRIM59.
Main Results:
- TRIM proteins significantly influence crosstalk within and between major cancer signaling pathways.
- Specific TRIM proteins, such as TRIM25, TRIM28, and TRIM59, have identified protein partners that act as master regulators of cancer signaling.
Conclusions:
- Understanding TRIM protein interactions within signaling networks is crucial for developing novel cancer therapeutics.
- Targeting TRIM protein-protein interactions presents a promising strategy for future cancer drug discovery.
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