Browse
Submit Data
Databases
API
Help

Dataset Information

42 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

TRIM family proteins and their emerging roles in innate immunity.

ABSTRACT: The superfamily of tripartite motif-containing (TRIM) proteins is conserved throughout the metazoan kingdom and has expanded rapidly during vertebrate evolution; there are now more than 60 TRIM proteins known in humans and mice. Many TRIM proteins are induced by type I and type II interferons, which are crucial for many aspects of resistance to pathogens, and several are known to be required for the restriction of infection by lentiviruses. In this Review, we describe recent data that reveal broader antiviral and antimicrobial activities of TRIM proteins and discuss their involvement in the regulation of pathogen-recognition and transcriptional pathways in host defence.

SUBMITTER: Ozato K

PROVIDER: S-EPMC3433745 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

TRIM family proteins and their emerging roles in innate immunity.

Ozato Keiko K Shin Dong-Mi DM Chang Tsung-Hsien TH Morse Herbert C HC

Nature reviews. Immunology 20081101 11

The superfamily of tripartite motif-containing (TRIM) proteins is conserved throughout the metazoan kingdom and has expanded rapidly during vertebrate evolution; there are now more than 60 TRIM proteins known in humans and mice. Many TRIM proteins are induced by type I and type II interferons, which are crucial for many aspects of resistance to pathogens, and several are known to be required for the restriction of infection by lentiviruses. In this Review, we describe recent data that reveal bro ...[more]

PMID: 18836477

Similar Datasets

Substrate recognition by TRIM and TRIM-like proteins in innate immunity.

Project description:TRIM (Tripartite motif) and TRIM-like proteins have emerged as an important class of E3 ligases in innate immunity. Their functions range from activation or regulation of innate immune signaling pathway to direct detection and restriction of pathogens. Despite the importance, molecular mechanisms for many TRIM/TRIM-like proteins remain poorly characterized, in part due to challenges of identifying their substrates. In this review, we discuss several TRIM/TRIM-like proteins in RNA sensing pathways and viral restriction functions. We focus on those containing PRY-SPRY, the domain most frequently used for substrate recognition, and discuss emerging mechanisms that are commonly utilized by several TRIM/TRIM-like proteins to tightly control their interaction with the substrates.

| S-EPMC7572318 | biostudies-literature

TRIM family proteins: roles in proteostasis and neurodegenerative diseases.

Project description:Neurodegenerative diseases (NDs) are a diverse group of disorders characterized by the progressive degeneration of the structure and function of the central or peripheral nervous systems. One of the major features of NDs, such as Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD), is the aggregation of specific misfolded proteins, which induces cellular dysfunction, neuronal death, loss of synaptic connections and eventually brain damage. By far, a great amount of evidence has suggested that TRIM family proteins play crucial roles in the turnover of normal regulatory and misfolded proteins. To maintain cellular protein quality control, cells rely on two major classes of proteostasis: molecular chaperones and the degradative systems, the latter includes the ubiquitin-proteasome system (UPS) and autophagy; and their dysfunction has been established to result in various physiological disorders including NDs. Emerging evidence has shown that TRIM proteins are key players in facilitating the clearance of misfolded protein aggregates associated with neurodegenerative disorders. Understanding the different pathways these TRIM proteins employ during episodes of neurodegenerative disorder represents a promising therapeutic target. In this review, we elucidated and summarized the diverse roles with underlying mechanisms of members of the TRIM family proteins in NDs.

| S-EPMC9364147 | biostudies-literature

Emerging roles of FAM14 family members (G1P3/ISG 6-16 and ISG12/IFI27) in innate immunity and cancer.

Project description:Interferons (IFNs) manifest their cellular functions by regulating expression of target genes known collectively as IFN-stimulated genes (ISGs). The repertoires of ISGs vary slightly between cell types, but routinely include a core of common ISGs robustly upregulated in most IFN-treated cells. Here, we review the regulation and cellular functions of 2 related ISGs, ISG12 (IFI27) and G1P3 (ISG 6-16), that are commonly induced by IFNs in most, if not all, IFN-responsive cells. On the basis of sequence similarity, they are grouped together within the newly defined FAM14 family. Emerging data on ISG12 and G1P3 suggest that both are mitochondrial proteins with opposing activities on apoptosis that may influence the innate immune responses of IFNs. The G1P3 gene encodes a low molecular weight mitochondrial protein that may stabilize mitochondrial function and oppose apoptosis. In contrast, ISG12 expression may sensitize cells to apoptotic stimuli via mitochondrial membrane destabilization. On the basis of these results and differences in induction kinetics between ISG12 and G1P3, we have proposed a model for the role of these genes in mediating cellular activity of IFNs.

| S-EPMC6468951 | biostudies-literature

TRIM-mediated precision autophagy targets cytoplasmic regulators of innate immunity.

Project description:The present paradigms of selective autophagy in mammalian cells cannot fully explain the specificity and selectivity of autophagic degradation. In this paper, we report that a subset of tripartite motif (TRIM) proteins act as specialized receptors for highly specific autophagy (precision autophagy) of key components of the inflammasome and type I interferon response systems. TRIM20 targets the inflammasome components, including NLRP3, NLRP1, and pro-caspase 1, for autophagic degradation, whereas TRIM21 targets IRF3. TRIM20 and TRIM21 directly bind their respective cargo and recruit autophagic machinery to execute degradation. The autophagic function of TRIM20 is affected by mutations associated with familial Mediterranean fever. These findings broaden the concept of TRIMs acting as autophagic receptor regulators executing precision autophagy of specific cytoplasmic targets. In the case of TRIM20 and TRIM21, precision autophagy controls the hub signaling machineries and key factors, inflammasome and type I interferon, directing cardinal innate immunity response systems in humans.

| S-EPMC4576868 | biostudies-other

The E3-ligase TRIM family of proteins regulates signaling pathways triggered by innate immune pattern-recognition receptors.

Project description:Innate immunity conferred by the type I interferon is critical for antiviral defense. To date only a limited number of tripartite motif (TRIM) proteins have been implicated in modulation of innate immunity and anti-microbial activity. Here we report the complementary DNA cloning and systematic analysis of all known 75 human TRIMs. We demonstrate that roughly half of the 75 TRIM-family members enhanced the innate immune response and that they do this at multiple levels in signaling pathways. Moreover, messenger RNA levels and localization of most of these TRIMs were found to be altered during viral infection, suggesting that their regulatory activities are highly controlled at both pre- and posttranscriptional levels. Taken together, our data demonstrate a very considerable dedication of this large protein family to the positive regulation of the antiviral response, which supports the notion that this family of proteins evolved as a component of innate immunity.

| S-EPMC3584420 | biostudies-literature

Emerging Roles of MHC Class I Region-Encoded E3 Ubiquitin Ligases in Innate Immunity.

Project description:The major histocompatibility complex (MHC) class I (MHC-I) region contains a multitude of genes relevant to immune response. Multiple E3 ubiquitin ligase genes, including tripartite motif 10 (TRIM10), TRIM15, TRIM26, TRIM27, TRIM31, TRIM38, TRIM39, TRIM40, and RING finger protein 39 (RNF39), are organized in a tight cluster, and an additional two TRIM genes (namely TRIM38 and TRIM27) telomeric of the cluster within the MHC-I region. The E3 ubiquitin ligases encoded by these genes possess important roles in controlling the intensity of innate immune responses. In this review, we discuss the E3 ubiquitin ligases encoded within the MHC-I region, highlight their regulatory roles in innate immunity, and outline their potential functions in infection, inflammatory and autoimmune diseases.

| S-EPMC8222901 | biostudies-literature

Emerging Roles of Tripartite Motif-Containing Family Proteins (TRIMs) in Eliminating Misfolded Proteins.

Project description:Protein quality control (PQC) is pivotal for eukaryotic cells to eliminate misfolded proteins and maintain cellular homeostasis. A decreased or increased capacity of PQC is associated with various diseases, e.g., neurodegenerative diseases and cancers. Recently, increasing evidences have suggested that tripartite motif-containing family proteins (TRIMs) are the key players in PQC regulation. Most TRIMs are E3 ubiquitin ligases, such as TRIM11/19/25, which, through the ubiquitination modifications, can contribute to effectively remove the cellular misfolded proteins or protein aggregates via the UPS pathway. In this review, we summarized the participation of TRIM members in misfolded protein elimination through distinct pathways, including the ubiquitin-proteasome system (UPS), autophagy system, and ER-associated degradation (ERAD).

| S-EPMC7479839 | biostudies-literature

Targeting TRIM Proteins: A Quest towards Drugging an Emerging Protein Class.

Project description:The ubiquitylation machinery regulates several fundamental biological processes from protein homeostasis to a wide variety of cellular signaling pathways. As a consequence, its dysregulation is linked to diseases including cancer, neurodegeneration, and autoimmunity. With this review, we aim to highlight the therapeutic potential of targeting E3 ligases, with a special focus on an emerging class of RING ligases, named tri-partite motif (TRIM) proteins, whose role as targets for drug development is currently gaining pharmaceutical attention. TRIM proteins exert their catalytic activity as scaffolds involved in many protein-protein interactions, whose multidomains and adapter-like nature make their druggability very challenging. Herein, we give an overview of the current understanding of this class of single polypeptide RING E3 ligases and discuss potential targeting options.

| S-EPMC8251876 | biostudies-literature

Positive Selection and Duplication of Bat TRIM Family Proteins.

Project description:Bats have received increasing attention because of some unique biological features they possess. TRIM is a large family of proteins that participate in diverse cellular functions, such as antiviral immunity, DNA damage repair, tumor suppression, and aging. These functional areas appear to be highly consistent with the special characteristics of bats, such as tolerance to viruses and DNA damage generated in flight, low cancer incidence, and longevity. However, there is still a lack of systematic study of the TRIM family in bats. Here, we explored the TRIM family of bats using the genomes of 16 representative species. The results showed that the bat TRIM family contains 70 members, with 24 under positive selection and 7 duplicated. Additional transcriptomic analysis revealed the tissue-specific expressions of TRIM9, 46, 54, 55, 63, and 72. Additionally, following interferon or viral stimulation, TRIM orthologs associated with antiviral immunity reported in humans were also upregulated in bat cells. The present study systematically analyzed the composition, evolution, and expression of bat TRIM genes. It may provide a theoretical basis for studies of bat TRIM in the fields of antiviral immunity, longevity, and tolerance to DNA damage.

| S-EPMC10145180 | biostudies-literature

Emerging Roles of the TRIM E3 Ubiquitin Ligases MID1 and MID2 in Cytokinesis.

Project description:Ubiquitination is a post-translational modification that consists of ubiquitin attachment to target proteins through sequential steps catalysed by activating (E1), conjugating (E2), and ligase (E3) enzymes. Protein ubiquitination is crucial for the regulation of many cellular processes not only by promoting proteasomal degradation of substrates but also re-localisation of cellular factors and modulation of protein activity. Great importance in orchestrating ubiquitination relies on E3 ligases as these proteins recognise the substrate that needs to be modified at the right time and place. Here we focus on two members of the TRIpartite Motif (TRIM) family of RING E3 ligases, MID1, and MID2. We discuss the recent findings on these developmental disease-related proteins analysing the link between their activity on essential factors and the regulation of cytokinesis highlighting the possible consequence of alteration of this process in pathological conditions.

| S-EPMC6433704 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data