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Published on: July 22, 2020
TRIM29 in Cutaneous Squamous Cell Carcinoma
Che-Yuan Hsu1, Teruki Yanagi1, Hideyuki Ujiie1
1Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Abstract:
Tripartite motif (TRIM) proteins play important roles in a wide range of cell physiological processes, such as signal transduction, transcriptional regulation, innate immunity, and programmed cell death. TRIM29 protein, encoded by the ATDC gene, belongs to the RING-less group of TRIM protein family members. It consists of four zinc finger motifs in a B-box domain and a coiled-coil domain, and makes use of the B-box domain as E3 ubiquitin ligase in place of the RING. TRIM29 was found to be involved in the formation of homodimers and heterodimers in relation to DNA binding; additional studies have also demonstrated its role in carcinogenesis, DNA damage signaling, and the suppression of radiosensitivity. Recently, we reported that TRIM29 interacts with keratins and FAM83H to regulate keratin distribution. Further, in cutaneous SCC, the expression of TRIM29 is silenced by DNA methylation, leading to the loss of TRIM29 and promotion of keratinocyte migration. This paper reviews the role of TRIM family proteins in malignant tumors, especially the role of TRIM29 in cutaneous SCC.
Insights
Tripartite motif 29 (TRIM29) protein, encoded by the ATDC gene, is crucial in cell processes and cancer. Its silencing via DNA methylation promotes skin cancer cell migration.
Area of Science:
- Molecular Biology
- Oncology
- Cell Biology
Background:
- Tripartite motif (TRIM) proteins are vital regulators of cellular functions including immunity and cell death.
- TRIM29, an ATDC gene product, functions as an E3 ubiquitin ligase and is implicated in DNA damage, carcinogenesis, and radiosensitivity.
- TRIM29 interacts with keratins and FAM83H, influencing keratin distribution.
Purpose of the Study:
- To review the role of TRIM family proteins in malignant tumors.
- To specifically elucidate the function of TRIM29 in cutaneous squamous cell carcinoma (SCC).
Main Methods:
- Literature review of TRIM family proteins and TRIM29.
- Analysis of TRIM29's interactions with keratins and FAM83H.
- Examination of TRIM29's role in DNA methylation and keratinocyte migration in cutaneous SCC.
Main Results:
- TRIM29's involvement in DNA binding, dimerization, and signaling pathways related to DNA damage.
- TRIM29's role in suppressing radiosensitivity and its implication in carcinogenesis.
- Silencing of TRIM29 expression by DNA methylation in cutaneous SCC leads to loss of TRIM29 function and enhanced keratinocyte migration.
Conclusions:
- TRIM29 plays a significant role in malignant tumor development.
- Epigenetic silencing of TRIM29 by DNA methylation is a key mechanism promoting cutaneous SCC progression.
- Understanding TRIM29's function offers potential therapeutic targets for skin cancer.
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