TRIM Proteins in Cancer

2012 ◽  
pp. 77-91 ◽  
Author(s):  
Valeria Cambiaghi ◽  
Virginia Giuliani ◽  
Sara Lombardi ◽  
Cristiano Marinelli ◽  
Francesca Toffalorio ◽  
...  
Keyword(s):  
Trim Proteins

scholarly journals TRIM32 and Malin in Neurological and Neuromuscular Rare Diseases

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 820
Author(s):  
Lorena Kumarasinghe ◽  
Lu Xiong ◽  
Maria Adelaida Garcia-Gimeno ◽  
Elisa Lazzari ◽  
Pascual Sanz ◽  
...  
Keyword(s):  
Common Ancestor ◽  
Genetic Diseases ◽  
Ubiquitin Ligases ◽  
E3 Ubiquitin Ligases ◽  
Lafora Disease ◽  
C Terminus ◽  
Rare Genetic Diseases ◽  
Tripartite Motif ◽  
Trim Proteins ◽  
Ring E3

Tripartite motif (TRIM) proteins are RING E3 ubiquitin ligases defined by a shared domain structure. Several of them are implicated in rare genetic diseases, and mutations in TRIM32 and TRIM-like malin are associated with Limb-Girdle Muscular Dystrophy R8 and Lafora disease, respectively. These two proteins are evolutionary related, share a common ancestor, and both display NHL repeats at their C-terminus. Here, we revmniew the function of these two related E3 ubiquitin ligases discussing their intrinsic and possible common pathophysiological pathways.

Lentiviral Effector Pathways of TRIM Proteins

2014 ◽  
Vol 33 (4) ◽  
pp. 191-197 ◽  
Author(s):  
Filippo Turrini ◽  
Andrea Di Pietro ◽  
Elisa Vicenzi
Keyword(s):  
Effector Pathways ◽  
Trim Proteins

scholarly journals P029 TRIM 21 protects against ulcerative colitis and colitic cancer via smad7 inhibition

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S146-S146
Author(s):  
K B Hahm
Keyword(s):  
Ulcerative Colitis ◽  
Coiled Coil ◽  
Type I ◽  
Typical Structure ◽  
Th17 Cell Differentiation ◽  
Bowel Diseases ◽  
Colitic Cancer ◽  
Β Receptor ◽  
Trim Proteins

Abstract Background Proteins of the tripartite motif-containing (TRIM) superfamily are critical in a variety of biological processes in either innate immunity or eliminating invading pathogens, by which had been implicated in pathogenesis of autoimmune diseases including inflammatory bowel diseases. The typical structure of TRIM proteins contains a RING motif in the N-terminal end, followed by a B-box motif, a coiled-coil domain and a B30.2/PRYSPRY region in the C-terminal end led to the regulation of TGF-β anti-inflammatory cytokines, by which TRIM21 has been reported to regulate IBD negatively through inhibiting Th1/Th17 cell differentiation. Methods Since antisense oligonucleotide targeting smad7 was withdrawn from clinical trial due to insufficient efficacy, in this study, we generated TRIM21 overexpressed cell lines to study the binding of TRIM21 to smad7 as well as the regulation of consequent TGF-β receptor. Results TRIM21 significantly binds to smad7 as well as repressed levels of TGF-b type I/II receptor. SBE-luc and 3TP-luc assay showed significantly decreased activities under TRIM21 + TGF-β. Since TRIM21 contains ubiquitin ligase, PRYSPRY, TRIM21 with TGF-β significantly decreased TGFRII via UPL. These in vitro evidences that TRIM21 significantly repressed TGF-β after binding smad7 were validated with DSS-induced colitis and colitic cancer model. TRIM21 was significantly decreased in DSS-induced ulcerative colitis, whereas ameliorated colitis showed significant restoration of TRIM21 Conclusion Leading to conclusion that loss of TRIM21 led to significant bout of IBD.

scholarly journals TRIM proteins in neuroblastoma

2019 ◽  
Vol 39 (12) ◽  
Author(s):  
Yonghu Xu ◽  
Zihan Zhang ◽  
Guofeng Xu
Keyword(s):  
High Risk ◽  
Tumor Suppressor ◽  
Solid Tumor ◽  
Molecular Mechanisms ◽  
Tumor Suppressor Proteins ◽  
Human Cancers ◽  
Tripartite Motif ◽  
Tumor In Childhood ◽  
Trim Proteins

Abstract Neuroblastoma (NB) is the most common extracranial solid tumor in childhood. Outcome for children with high-risk NB remains unsatisfactory. Accumulating evidence suggests that tripartite motif (TRIM) family proteins express diversely in various human cancers and act as regulators of oncoproteins or tumor suppressor proteins. This review summarizes the TRIM proteins involving in NB and the underlying molecular mechanisms. We expect these new insights will provide important implications for the treatment of NB by targeting TRIM proteins.

scholarly journals Identification of a Shrimp E3 Ubiquitin Ligase TRIM50-Like Involved in Restricting White Spot Syndrome Virus Proliferation by Its Mediated Autophagy and Ubiquitination

2021 ◽  
Vol 12 ◽  
Author(s):  
Chao Zhao ◽  
Chao Peng ◽  
Pengfei Wang ◽  
Lulu Yan ◽  
Sigang Fan ◽  
...  
Keyword(s):  
White Spot Syndrome Virus ◽  
Penaeus Monodon ◽  
White Spot ◽  
Positive Role ◽  
Protein Levels ◽  
Mrna And Protein Expression ◽  
White Spot Syndrome ◽  
Critical Components ◽  
Trim Proteins

Most tripartite motif (TRIM) family proteins are critical components of the autophagy machinery and play important roles in host defense against viral pathogens in mammals. However, the roles of TRIM proteins in autophagy and viral infection have not been studied in lower invertebrates, especially crustaceans. In this study, we first identified a TRIM50-like gene from Penaeus monodon (designated PmTRIM50-like), which, after a white spot syndrome virus (WSSV) challenge, was significantly upregulated at the mRNA and protein levels in the intestine and hemocytes. Knockdown of PmTRIM50-like led to an increase in the WSSV quantity in shrimp, while its overexpression led to a decrease compared with the controls. Autophagy can be induced by WSSV or rapamycin challenge and has been shown to play a positive role in restricting WSSV replication in P. monodon. The mRNA and protein expression levels of PmTRIM50-like significantly increased with the enhancement of rapamycin-induced autophagy. The autophagy activity induced by WSSV or rapamycin challenge could be inhibited by silencing PmTRIM50-like in shrimp. Further studies showed that rapamycin failed to induce autophagy or inhibit WSSV replication after knockdown of PmTRIM50-like. Moreover, pull-down and in vitro ubiquitination assays demonstrated that PmTRIM50-like could interact with WSSV envelope proteins and target them for ubiquitination in vitro. Collectively, this study demonstrated that PmTRIM50-like is required for autophagy and is involved in restricting the proliferation of WSSV through its ubiquitination. This is the first study to report the role of a TRIM family protein in virus infection and host autophagy in crustaceans.

scholarly journals The Roles of TRIMs in Antiviral Innate Immune Signaling

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhou Shen ◽  
Lin Wei ◽  
Zhi-bo Yu ◽  
Zhi-yan Yao ◽  
Jing Cheng ◽  
...  
Keyword(s):  
Immune Response ◽  
Lupus Erythematosus ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Cellular Functions ◽  
Trim Protein ◽  
Innate Immune Signaling ◽  
Viral Lifecycle ◽  
Trim Proteins ◽  
Viral Components

The Tripartite motif (TRIM) protein family, which contains over 80 members in human sapiens, is the largest subfamily of the RING-type E3 ubiquitin ligase family. It is implicated in regulating various cellular functions, including cell cycle process, autophagy, and immune response. The dysfunction of TRIMs may lead to numerous diseases, such as systemic lupus erythematosus (SLE). Lots of studies in recent years have demonstrated that many TRIM proteins exert antiviral roles. TRIM proteins could affect viral replication by regulating the signaling pathways of antiviral innate immune responses. Besides, TRIM proteins can directly target viral components, which can lead to the degradation or functional inhibition of viral protein through degradative or non-degradative mechanisms and consequently interrupt the viral lifecycle. However, new evidence suggests that some viruses may manipulate TRIM proteins for their replication. Here, we summarize the latest discoveries on the interactions between TRIM protein and virus, especially TRIM proteins’ role in the signaling pathway of antiviral innate immune response and the direct “game” between them.

scholarly journals The Adenovirus E4 ORF3 Protein Binds and Reorganizes the TRIM Family Member Transcriptional Intermediary Factor 1 Alpha

2007 ◽  
Vol 81 (8) ◽  
pp. 4264-4271 ◽  
Author(s):  
Mark A. Yondola ◽  
Patrick Hearing
Keyword(s):  
Family Member ◽  
Protein Interactions ◽  
Coiled Coil ◽  
Ring Finger ◽  
Nuclear Bodies ◽  
Reading Frame ◽  
Orf3 Protein ◽  
Proteomic Approach ◽  
Evolutionarily Conserved ◽  
Trim Proteins

ABSTRACT One of the most interesting functions attributed to the adenovirus early region 4 open reading frame 3 (E4 ORF3) protein is its reorganization of promyelocytic leukemia (PML) protein nuclear bodies. These normally punctate structures are reorganized by E4 ORF3 into tracks that eventually surround viral replication centers. PML rearrangement is an evolutionarily conserved function of E4 ORF3, yet its cause and functional relevance remain mysteries. The E4 ORF3 protein coimmunoprecipitates with the PML protein, yet E4 ORF3 still forms tracks in cells that lack PML. The PML protein is a member of a larger protein family termed tripartite motif (TRIM) proteins. TRIM proteins contain a tripartite domain structure in proximity to their N termini that consists of a RING finger domain, followed by one or two B box domains and a C-terminal coiled-coil domain (collectively termed the RBCC domain). The order and spacing of these domains are evolutionarily conserved and thought to mediate protein-protein interactions and other functions. We implemented a proteomic approach to isolate cellular proteins that bind to E4 ORF3. We identified a novel interaction between E4 ORF3 and another TRIM family member, transcriptional intermediary factor 1 alpha (TIF1α). TIF1α functions by recruiting coactivators and/or corepressors to modulate transcription. The interaction between E4 ORF3 and TIF1α was validated by coimmunoprecipitation and binding of recombinant proteins. Indirect immunofluorescence assays demonstrated that TIF1α is reorganized into track structures that contain PML upon E4 ORF3 expression. The RBCC domain of TIF1α is sufficient for E4 ORF3-induced rearrangement, and TIF1α reorganization is conserved across adenovirus serotypes.

scholarly journals E3 Ubiquitin Ligase TRIM Proteins, Cell Cycle and Mitosis

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 510 ◽  
Author(s):  
Santina Venuto ◽  
Giuseppe Merla
Keyword(s):  
Cell Cycle ◽  
Cancer Progression ◽  
Current Knowledge ◽  
Ubiquitin Ligases ◽  
Cell Protein ◽  
E3 Ubiquitin Ligases ◽  
Daughter Cells ◽  
Protein Ubiquitination ◽  
Functional Units ◽  
Trim Proteins

The cell cycle is a series of events by which cellular components are accurately segregated into daughter cells, principally controlled by the oscillating activities of cyclin-dependent kinases (CDKs) and their co-activators. In eukaryotes, DNA replication is confined to a discrete synthesis phase while chromosome segregation occurs during mitosis. During mitosis, the chromosomes are pulled into each of the two daughter cells by the coordination of spindle microtubules, kinetochores, centromeres, and chromatin. These four functional units tie chromosomes to the microtubules, send signals to the cells when the attachment is completed and the division can proceed, and withstand the force generated by pulling the chromosomes to either daughter cell. Protein ubiquitination is a post-translational modification that plays a central role in cellular homeostasis. E3 ubiquitin ligases mediate the transfer of ubiquitin to substrate proteins determining their fate. One of the largest subfamilies of E3 ubiquitin ligases is the family of the tripartite motif (TRIM) proteins, whose dysregulation is associated with a variety of cellular processes and directly involved in human diseases and cancer. In this review we summarize the current knowledge and emerging concepts about TRIMs and their contribution to the correct regulation of cell cycle, describing how TRIMs control the cell cycle transition phases and their involvement in the different functional units of the mitotic process, along with implications in cancer progression.

scholarly journals TRIM Proteins and Their Roles in the Influenza Virus Life Cycle

2020 ◽  
Vol 8 (9) ◽  
pp. 1424
Author(s):  
Hye-Ra Lee ◽  
Myoung Kyu Lee ◽  
Chan Woo Kim ◽  
Meehyein Kim
Keyword(s):  
Influenza Virus ◽  
Signaling Pathways ◽  
Viral Infections ◽  
Influenza Virus Infection ◽  
Ubiquitin Proteasome System ◽  
Viral Propagation ◽  
Cellular Processes ◽  
Ubiquitin Proteasome ◽  
Immune Sensing ◽  
Trim Proteins

The ubiquitin-proteasome system (UPS) has been recognized for regulating fundamental cellular processes, followed by induction of proteasomal degradation of target proteins, and triggers multiple signaling pathways that are crucial for numerous aspects of cellular physiology. Especially tripartite motif (TRIM) proteins, well-known E3 ubiquitin ligases, emerge as having critical roles in several antiviral signaling pathways against varying viral infections. Here we highlight recent advances in the study of antiviral roles of TRIM proteins toward influenza virus infection in terms of the modulation of pathogen recognition receptor (PRR)-mediated innate immune sensing, direct obstruction of influenza viral propagation, and participation in virus-induced autophagy.

scholarly journals Biochemical and Biophysical Characterization of a Chimeric TRIM21-TRIM5α Protein

2008 ◽  
Vol 82 (23) ◽  
pp. 11669-11681 ◽  
Author(s):  
Alak Kanti Kar ◽  
Felipe Diaz-Griffero ◽  
Yuan Li ◽  
Xing Li ◽  
Joseph Sodroski
Keyword(s):  
Variable Region ◽  
Globular Structure ◽  
Biophysical Characterization ◽  
Immunodeficiency Virus ◽  
Infected Insect ◽  
Low Levels ◽  
Trim Proteins

ABSTRACT The tripartite motif (TRIM) protein, TRIM5α, is an endogenous factor in primates that recognizes the capsids of certain retroviruses after virus entry into the host cell. TRIM5α promotes premature uncoating of the capsid, thus blocking virus infection. Low levels of expression and tendencies to aggregate have hindered the biochemical, biophysical, and structural characterization of TRIM proteins. Here, a chimeric TRIM5α protein (TRIM5Rh-21R) with a RING domain derived from TRIM21 was expressed in baculovirus-infected insect cells and purified. Although a fraction of the TRIM5Rh-21R protein formed large aggregates, soluble fractions of the protein formed oligomers (mainly dimers), exhibited a protease-resistant core, and contained a high percentage of helical secondary structure. Cross-linking followed by negative staining and electron microscopy suggested a globular structure. The purified TRIM5Rh-21R protein displayed E3-ligase activity in vitro and also self-ubiquitylated in the presence of ubiquitin-activating and -conjugating enzymes. The purified TRIM5Rh-21R protein specifically associated with human immunodeficiency virus type 1 capsid-like complexes; a deletion within the V1 variable region of the B30.2(SPRY) domain decreased capsid binding. Thus, the TRIM5Rh-21R restriction factor can directly recognize retroviral capsid-like complexes in the absence of other mammalian proteins.

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