Tripartite Motif Protein Family Research Articles

Targeting TRIM26: Unveiling an Oncogene and Identification of Plant Metabolites as a Potential Therapeutics for Breast Cancer.

Breast cancer is the major cause of cancer-related mortality and frequent malignancies among women worldwide. The TRIM (Tripartite Motif) protein family is a broad and diverse set of proteins that contain a conserved structural motif known as the tripartite motif, which comprises of three different domains, B-box domain, Coiled-coil domain and RBR (Ring-finger, B-box, and coiled-coil) domain. TRIM proteins are involved in regulating cancer growth and metastasis. However, TRIM proteins are still unexplored in cancer cell regulation. In this study, by using a cancer database expression of all TRIM proteins was determined in breast cancer. Out of 77 TRIM genes, 16 genes were upregulated in breast cancer. Here, the upregulated TRIM26 gene's role is not yet explored in breast cancer. Indeed, TRIM26 is upregulated in 21 cancer types out of 33 cancer types. To investigate the role of TRIM26 in breast cancer, siRNA-mediated gene silencing was carried out in MCF-7 and MDA-MB 231 breast cancer cells. Reduced expression of TRIM 26 decreased cancer cell proliferation, migration and invasion with simultaneous reduction of various proliferative, cell cycle and mesenchymal markers and upregulation of epithelial markers. Further, docking studies found potential novel plant metabolites. Thus, targeting TRIM26 may provide a novel therapeutic approach for breast cancer treatment.

MG53 suppresses tumor growth via transcriptional inhibition of KIF11 in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) poses a formidable challenge in oncology due to its limited treatment options and poor long-term survival rates. Our previous work identified MG53, a member of the tripartite motif family protein (TRIM72), as a key player in tissue repair with potential applications in regenerative medicine. Despite the focus on MG53’s cytosolic functions, its nuclear role in suppressing pancreatic cancer remains unknown. Through orthotopic and subcutaneous transplantation studies in mice, we observed enhanced tumor growth in MG53-deficient mice compared to wild-type counterparts. The overexpression of KIF11, a motor protein crucial for cell mitosis regulation, has been linked to the aggressive proliferation of pancreatic cancer cells. Confocal imaging confirmed MG53′s presence in the nucleus of human pancreatic cancer cells, while functional assays demonstrated its impact on KIF11 expression and subsequent cell proliferation. Mechanistically, we revealed MG53′s transcriptional control over KIF11, leading to cell cycle arrest. Our findings position MG53 as a promising tumor suppressor in PDAC, offering a novel avenue for therapeutic intervention by regulating KIF11 expression.

The Role of Tripartite Motif Family Proteins in Chronic Liver Diseases: Molecular Mechanisms and Therapeutic Potential.

The worldwide impact of liver diseases is increasing steadily, with a consistent upswing evidenced in incidence and mortality rates. Chronic liver diseases (CLDs) refer to the liver function's progressive deterioration exceeding six months, which includes abnormal clotting factors, detoxification failure, and hepatic cholestasis. The most common etiologies of CLDs are mainly composed of chronic viral hepatitis, MAFLD/MASH, alcoholic liver disease, and genetic factors, which induce inflammation and harm to the liver, ultimately resulting in cirrhosis, the irreversible final stage of CLDs. The latest research has shown that tripartite motif family proteins (TRIMs) function as E3 ligases, which participate in the progression of CLDs by regulating gene and protein expression levels through post-translational modification. In this review, our objective is to clarify the molecular mechanisms and potential therapeutic targets of TRIMs in CLDs and provide insights for therapy guidelines and future research.

Emerging roles of tripartite motif family proteins (TRIMs) in breast cancer.

Breast cancer (BC) is the most common malignant tumor worldwide. Despite enormous progress made in the past decades, the underlying mechanisms of BC remain further illustrated. Recently, TRIM family proteins proved to be engaged in BC progression through regulating various aspects. Here we reviewed the structures and basic functions of TRIM family members and first classified them into three groups according to canonical polyubiquitination forms that they could mediate: K48- only, K63- only, and both K48- and K63-linked ubiquitination. Afterwards, we focused on the specific biological functions and mechanisms of TRIMs in BCs, including tumorigenesis and invasiveness, drug sensitivity, tumor immune microenvironment (TIME), cell cycle, and metabolic reprogramming. We also explored the potential of TRIMs as novel biomarkers for predicting prognosis and future therapeutic targets in BC.

Association of the TRIM family protein with survival outcomes and clinicopathological features in colorectal cancer: a systematic review and meta-analysis

BackgroundThe tripartite motif (TRIM) proteins have been reported to play crucial roles in various malignancies. However, the clinical significance of TRIM proteins in colorectal cancer (CRC) remains controversial. This study aimed to evaluate the association between TRIM proteins and the clinicopathological features and survival outcomes in patients with CRC.MethodsWe performed a meta-analysis to investigate whether TRIM is a prognostic factor in CRC. PubMed, Embase, Web of Science, CNKI and Weipu databases were searched to identify eligible studies that evaluated the association between TRIM proteins and overall survival (OS), as well as the clinicopathological features of patients with CRC. Hazard ratios (HR) or odds ratios (OR) with 95% confidence interval (CI) were derived and pooled using a fixed-effects model.ResultsFrom inception to March 2023, we extracted study characteristics and prognostic data for each identified study. Twelve studies enrolling 1608 patients were eligible for inclusion. Data on OS and recurrence-free survival (RFS) were available for 12 and 2 studies, respectively. The pooled analysis results showed a significant correlation between the elevated TRIM proteins and shorter OS (HR = 2.42, 95% CI: 1.96–2.99) and worse RFS (HR = 2.51, 95% CI: 1.78–3.54) in patients with CRC. The combined ORs indicated that TRIM protein over-expression was significantly associated with advanced TNM stage (OR = 2.26, 95% CI: 1.25–4.10), deep tumor invasion (OR = 2.01, 95% CI: 1.04–3.88), lymph node metastasis (OR = 2.99, 95% CI: 2.19–4.09) and perineural invasion (OR = 1.95, 95% CI: 1.18–3.23).ConclusionsOur findings suggest that TRIM proteins can predict tumor progression and poor prognosis in CRC. Therefore, TRIM proteins may be promising therapeutic targets for patients with CRC.Graphical

MG53/TRIM72: multi-organ repair protein and beyond.

MG53, a member of the tripartite motif protein family, possesses multiple functionalities due to its classic membrane repair function, anti-inflammatory ability, and E3 ubiquitin ligase properties. Initially recognized for its crucial role in membrane repair, the therapeutic potential of MG53 has been extensively explored in various diseases including muscle injury, myocardial damage, acute lung injury, and acute kidney injury. However, further research has revealed that the E3 ubiquitin ligase characteristics of MG53 also contribute to the pathogenesis of certain conditions such as diabetic cardiomyopathy, insulin resistance, and metabolic syndrome. Moreover, recent studies have highlighted the anti-tumor effects of MG53 in different types of cancer, such as small cell lung cancer, liver cancer, and colorectal cancer; these effects are closely associated with their E3 ubiquitin ligase activities. In summary, MG53 is a multifunctional protein that participates in important physiological and pathological processes of multiple organs and is a promising therapeutic target for various human diseases. MG53 plays a multi-organ protective role due to its membrane repair function and its exertion of anti-tumor effects due to its E3 ubiquitin ligase properties. In addition, the controversial aspect of MG53's E3 ubiquitin ligase properties potentially causing insulin resistance and metabolic syndrome necessitates further cross-validation for clarity.

TRIM72 restricts lyssavirus infection by inducing K48-linked ubiquitination and proteasome degradation of the matrix protein.

The tripartite motif (TRIM) protein family is the largest subfamily of E3 ubiquitin ligases, playing a crucial role in the antiviral process. In this study, we found that TRIM72, a member of the TRIM protein family, was increased in neuronal cells and mouse brains following rabies lyssavirus (RABV) infection. Over-expression of TRIM72 significantly reduced the viral titer of RABV in neuronal cells and mitigated the pathogenicity of RABV in mice. Furthermore, we found that TRIM72 over-expression effectively prevents the assembly and/or release of RABV. In terms of the mechanism, TRIM72 promotes the K48-linked ubiquitination of RABV Matrix protein (M), leading to the degradation of M through the proteasome pathway. TRIM72 directly interacts with M and the interaction sites were identified and confirmed through TRIM72-M interaction model construction and mutation analysis. Further investigation revealed that the degradation of M induced by TRIM72 was attributed to TRIM72's promotion of ubiquitination at site K195 in M. Importantly, the K195 site was found to be partially conserved among lyssavirus's M proteins, and TRIM72 over-expression induced the degradation of these lyssavirus M proteins. In summary, our study has uncovered a TRIM family protein, TRIM72, that can restrict lyssavirus replication by degrading M, and we have identified a novel ubiquitination site (K195) in lyssavirus M.

TRIM58 functions as a tumor suppressor in colorectal cancer by promoting RECQL4 ubiquitination to inhibit the AKT signaling pathway

BackgroundThis study aimed to investigate the underlying molecular mechanisms of TRIM58 in the development of colorectal cancer (CRC). CRC is one of the most common cancers of the digestive tract worldwide. The ubiquitin–proteasome system regulates many oncogenic or tumor-suppressive proteins. TRIM58, an E3 ubiquitin ligase and a member of the tripartite motif protein family, is a potential prognostic marker that indicates poor prognosis in cancer. Currently, the precise molecular mechanisms for the TRIM58-mediated CRC progression remain unclear.MethodsTo examine the effects of TRIM58 on cell viability, cell cycle progression, and apoptosis in CRC, Cell Counting Kit-8 and flow cytometry assays were employed. The AKT inhibitor LY294002 was used to examine the effects of AKT signaling on TRIM58-mediated cell viability, cell cycle progression, and apoptosis in CRC. Additionally, Co-IP and ubiquitination assays were used to examine the correlation between TRIM58 and RECQL4.ResultsTRIM58 overexpression inhibited CRC cell viability and promoted cell cycle arrest and apoptosis, in which the TRIM58 knockdown demonstrated inversed effects via the AKT signaling pathway. TRIM58 inhibited RECQL4 protein levels through its ubiquitin ligase activity, and RECQL4 overexpression inhibited TRIM58 overexpression-mediated CRC cell viability, cell cycle progression, and apoptosis. The downregulation of TRIM58 and upregulation of RECOL4 were observed in human CRC tissue, and TRIM58 demonstrated antitumor effects in CRC-induced tumor growth in a mouse model.ConclusionsTRIM58 acts as a tumor suppressor in CRC through the promotion of RECQL4 ubiquitination and inhibition of the AKT signaling pathway and may be investigated for the successful treatment of CRC.

Comprehensive Analysis of the Prognostic Significance of the TRIM Family in the Context of TP53 Mutations in Cancers.

The p53 protein is an important tumor suppressor, and TP53 mutations are frequently associated with poor prognosis in various cancers. Mutations in TP53 result in a loss of p53 function and enhanced expression of cell cycle genes, contributing to the development and progression of cancer. Meanwhile, several tripartite motif (TRIM) proteins are known to regulate cell growth and cell cycle transition. However, the prognostic values between TP53 and TRIM family genes in cancer are unknown. In this study, we analyzed the relationship between the TP53 mutations and TRIM family proteins and evaluated the prognostic significance of TRIM family proteins in cancer patients with P53 mutations. Our findings identified specific TRIM family members that are upregulated in TP53 mutant tumors and are associated with the activation of genes related to a cell-cycle progression in the context of TP53 mutations.

Abstract 1729: MG53 suppresses the tumor growth via transcriptional inhibiting the expression of KIF11 in pancreatic cancer

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with limited therapeutic options and a dismal long-term survival. The upregulation of KIF11, a motor protein that regulates cell mitosis, has been associated with the aggressive proliferation of pancreatic cancer cells. A molecular strategy to counteract the hyperactivity of KIF11 may represent a potential means to treat PDAC. We previously identified MG53, a member of the tripartite motif family protein (TRIM72), as an important component of tissue repair, and revealed its potential application in regenerative medicine. So far, most published studies have focused on the cytosolic and vesicle-trafficking function of MG53, little is known on the nuclear action of MG53 in pancreatic tumor suppression. In the present study, our confocal imaging revealed frequent appearance of MG53 in the nucleus of human pancreatic cancer cells, and subcellular fractionation assay showed that a majority of MG53 protein was present in the nuclear fraction. Decreased MG53 and increased KIF11 protein expression were observed in both pancreatic cancer cell lines (PANC-1 and mPanc96) and PDAC tissue from surgically resected tumors. Overexpressing MG53 inhibited colony formation and proliferation of PANC-1 cells with significant reduction of KIF11 expression. Furthermore, we demonstrated that MG53-mediated control of KIF11 expression occurs at the gene transcription level. Chromatin immunoprecipitation demonstrated an interaction between MG53 and the promoter of KIF11 in PANC-1 cells. Using a luciferase cell reporter driven by the KIF11 promoter, we found that overexpressing MG53 led to downregulation of the KIF11 transcription activity, and induced cell cycle arrest at the G2/M phase. We also conducted syngeneic orthotopic transplantation of a mouse pancreatic cancer cell line, KPC cells derived from pancreatic tumor in KRasG12D/Trp53-/-/Pdx-1-Cre (KPC) mice, into the pancreas of wild type (WT) and mg53-/- (MG53-KO) mice, which showed aggressive pancreatic tumor growth in MG53-KO mice compared with WT mice after 3-week of transplantation. Western blots revealed that a considerable amount of MG53 protein was found in the pancreatic tumors derived from KPCs in WT mice vs. those in MG53-KO mice, indicating the accumulation of circulating MG53 during tumor growth. Overall, these findings demonstrated that MG53 functions as a tumor suppressor to inhibit cancer cell proliferation and the tumor growth through transcriptional down-regulating the expression of KIF11 in pancreatic cancer, and provided a new therapeutic target for the treatment of patients with PDAC. Citation Format: Xiao-Liang Wang, Xiangfei He, Zobeida Cruz-Monserrate, Allen Tsung, Jianjie Ma, Chuanxi Cai. MG53 suppresses the tumor growth via transcriptional inhibiting the expression of KIF11 in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1729.

Tripartite Motif Protein Family in Central Nervous System Diseases.

Tripartite motif (TRIM) protein superfamily is a group of E3 ubiquitin ligases characterized by the conserved RING domain, the B-box domain, and the coiled-coil domain (RBCC). It is widely involved in various physiological and pathological processes, such as intracellular signal transduction, cell cycle regulation, oncogenesis, and innate immune response. Central nervous system (CNS) diseases are composed of encephalopathy and spinal cord diseases, which have a high disability and mortality rate. Patients are often unable to take care of themselves and their life quality can be seriously declined. Initially, the function research of TRIM proteins mainly focused on cancer. However, in recent years, accumulating attention is paid to the roles they play in CNS diseases. In this review, we integrate the reported roles of TRIM proteins in the pathological process of CNS diseases and related signaling pathways, hoping to provide theoretical bases for further research in treating CNS diseases targeting TRIM proteins. TRIM proteins participated in CNS diseases. TRIM protein family is characterized by a highly conserved RBCC domain, referring to the RING domain, the B-box domain, and the coiled-coil domain. Recent research has discovered the relations between TRIM proteins and various CNS diseases, especially Alzheimer's disease, Parkinson's disease, and ischemic stroke.

The Functions of TRIM56 in Antiviral Innate Immunity and Tumorigenesis

As a member of the TRIM (tripartite motif) protein family, TRIM56 can function as an E3 ubiquitin ligase. In addition, TRIM56 has been shown to possess deubiquitinase activity and the ability to bind RNA. This adds to the complexity of the regulatory mechanism of TRIM56. TRIM56 was initially found to be able to regulate the innate immune response. In recent years, its role in direct antiviral and tumor development has also attracted the interest of researchers, but there is no systematic review on TRIM56. Here, we first summarize the structural features and expression of TRIM56. Then, we review the functions of TRIM56 in TLR and cGAS-STING pathways of innate immune response, the mechanisms and structural specificity of TRIM56 against different types of viruses, and the dual roles of TRIM56 in tumorigenesis. Finally, we discuss the future research directions regarding TRIM56.

TRIM58 Interacts with ZEB1 to Suppress NSCLC Tumor Malignancy by Promoting ZEB1 Protein Degradation via UPP.

Currently, how to successfully control refractory and metastatic diseases remains a fundamental goal for clinicians to improve therapeutic effects for patients with non-small cell lung cancer (NSCLC). Several studies have discovered that TRIM58, a member of tripartite motif protein family, shows antitumor effect in multiple types of cancer. In this study, we aimed to further clarify the molecular regulatory network of TRIM58 and corresponding targets for NSCLC patients. TRIM58 expression in clinical tumor tissue samples and cancer cell lines was examined. Functional experiments including cellular invasion, cell metastasis, chemoresistance assay, and ubiquitination evaluation experiments were conducted to investigate the interaction between TRIM58 and ZEB1, which is a prime element of transcription factor network that controls epithelial-to-mesenchymal transition. TRIM58 expression was characteristically decreased in NSCLC tumor tissues and cancer cell lines. Functional experiments demonstrated that TRIM58 suppression enhanced malignant biological behaviors including cellular survivability, migration, and invasion, as well as stem-like cellular phenotype of tumor cells. TRIM58 silencing also significantly enhanced the chemoresistance of NSCLC cells to chemoagents. TRIM58-ZEB1 interaction accelerated degradation of ZEB1 protein, thus further leading to the augment of tumor behaviors. Further detailed molecular experiments revealed that the interaction between TRIM58 and ZEB1 was mediated via ubiquitin-proteasome pathway (UPP). TRIM58 suppressed NSCLC through interacting with ZEB1 and promoting ZEB1 protein degradation via UPP. The present research sheds light on the interaction between TRIM58 and ZEB1, and TRIM58/ZEB1 axis might be the potential therapeutic targets of NSCLC.

Research progress of TRIMs protein family in tumors

The tripartite motif (TRIMs) protein family has E3 ubiquitin ligase activity among most of its members. They participate in multiple cellular processes and signaling pathways in living organisms, including cell cycle, growth, and metabolism, and mediate chromatin modification, transcriptional regulation, post-translational modification, and cellular autophagy. Previous studies have confirmed that the TRIMs protein family is involved in the development of various cancers and correlated with the prognosis of tumor patients. Here we summarize the biological roles of the TRIMs protein family in cancers.

TRIM proteins in breast cancer: Function and mechanism

Breast cancer is the most prevalent malignancy in the world, and despite tremendous progress in current treatment strategies, recurrence, metastasis and drug resistance of breast cancer remain the major causes of death in patients. Tripartite motif (TRIM) family proteins play a critical role in the tumor progression such as cell proliferation, migration, invasion, and metastasis. Accumulating evidence suggests that the TRIM protein family serve as cancer suppressor proteins or oncoproteins in breast cancer. This review focused on the roles and molecular mechanisms of TRIM protein in breast cancer. Importantly, it provides new insights that TRIM proteins may be ideal targets to treat breast cancer.

Identification of Histone Peptide Binding Specificity and Small-Molecule Ligands for the TRIM33α and TRIM33β Bromodomains.

TRIM33 is a member of the tripartite motif (TRIM) family of proteins, some of which possess E3 ligase activity and are involved in the ubiquitin-dependent degradation of proteins. Four of the TRIM family proteins, TRIM24 (TIF1α), TRIM28 (TIF1β), TRIM33 (TIF1γ) and TRIM66, contain C-terminal plant homeodomain (PHD) and bromodomain (BRD) modules, which bind to methylated lysine (KMen) and acetylated lysine (KAc), respectively. Here we investigate the differences between the two isoforms of TRIM33, TRIM33α and TRIM33β, using structural and biophysical approaches. We show that the N1039 residue, which is equivalent to N140 in BRD4(1) and which is conserved in most BRDs, has a different orientation in each isoform. In TRIM33β, this residue coordinates KAc, but this is not the case in TRIM33α. Despite these differences, both isoforms show similar affinities for H31–27K18Ac, and bind preferentially to H31–27K9Me3K18Ac. We used this information to develop an AlphaScreen assay, with which we have identified four new ligands for the TRIM33 PHD-BRD cassette. These findings provide fundamental new information regarding which histone marks are recognized by both isoforms of TRIM33 and suggest starting points for the development of chemical probes to investigate the cellular function of TRIM33.

The inhibition of TRIM35-mediated TIGAR ubiquitination enhances mitochondrial fusion and alleviates renal ischemia-reperfusion injury

Tripartite motif 35 (TRIM35) is a member of the tripartite motif protein family and has been recognized to play a key role in immune-inflammatory diseases. However, the role of TRIM35 in renal ischemia-reperfusion injury (IRI) remains unclear. Our study proved that knockdown of TRIM35 alleviates kidney IRI by inhibiting oxidative stress and enhancing mitochondrial fusion. In addition, our experimental results found that TRIM35 interacts with TP53-induced glycolysis and apoptosis regulator (TIGAR) and promotes the polyubiquitination of TIGAR and induces its degradation in the proteasome pathway. Furthermore, TIGAR knockdown significantly inhibited mitochondrial fusion. These results indicate that TRIM35 is a potential therapeutic target for renal IRI.

Tripartite motif family proteins in inflammatory bowel disease: Mechanisms and potential for interventions.

Inflammatory bowel disease (IBD) is a chronic recurrent gastrointestinal inflammatory disease that poses a heavy burden to the global healthcare system. However, the current paucity of mechanistic understanding of IBD pathogenesis hampers the development of aetiology‐directed therapies. Novel therapeutic options based on IBD pathogenesis are urgently needed for attaining better long‐term prognosis for IBD patients. The tripartite motif (TRIM) family is a large protein family including more than 70 structurally conservative members, typically characterized by their RBCC structure, which primarily function as E3 ubiquitin ligases in post‐translational modification. They have emerged as regulators of a broad range of cellular mechanisms, including proliferation, differentiation, transcription and immune regulation. TRIM family proteins are involved in multiple diseases, such as viral infection, cancer and autoimmune disorders, including inflammatory bowel disease. This review provides a comprehensive perspective on TRIM proteins' involvement in the pathophysiology and progression of IBD, in particular, on intestinal mucosal barriers, gene susceptibility and opportunistic infections, thus providing novel therapeutic targets for this complicated disease. However, the exact mechanisms of TRIM proteins in IBD pathogenesis and IBD‐related carcinogenesis are still unknown, and more studies are warranted to explore potential therapeutic targets of TRIM proteins in IBD.

Identification Prognostic Value and Correlation with Tumor-Infiltrating Immune Cells of Tripartite-Motif Family Genes in Hepatocellular Carcinoma.

BackgroundHepatocellular carcinoma (HCC) is one of the most common and mortality types of malignant tumors in the world. The Tripartite-Motif (TRIM) protein family consists of more than 80 proteins with E3 ubiquitin ligase activity. Increasing studies have found that TRIM family proteins play an extremely important role in the occurrence and development of tumors. However, the expression and prognostic values of TRIMs in HCC have not been clarified.MethodsWe used bioinformatic methods to explore the potential function of TRIM family genes in the HCC. Web servers ONCOMINE, UALCAN, GEPIA, cBioPortal, STRING, DAVID 6.8 and TIMER were used in this research.ResultsWe screened TRIM1-76 and found the expressions of TRIM6, TRIM11, TRIM16, TRIM18(MID1), TRIM24, TRIM28, TRIM31, TRIM37, TRIM45, TRIM52, TRIM59, TRIM66 were significantly changed in HCC. Among them, TRIM24, TRIM28, TRIM37, TRIM45 and TRIM59 had significant effects on pathological stages, overall survival and disease free survival. Functions of these genes are primarily related to transcriptional misregulation in cancer, p53 signaling pathway, alcoholism and viral carcinogenesis, FoxO signal pathway, PI3K-AKT pathway, cell cycle, microRNAs in cancer. Our results showed the significant correlation between TRIMs expression and infiltration of innate immune cells (macrophages, neutrophils, and dendritic cells).ConclusionOur result provides novel insights into the function of TRIM family genes, which may be used as potential references for drug targets and accurate survival predictions in patients with HCC.

TRIM29 in Cutaneous Squamous Cell Carcinoma.

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.