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Results for “TRIM21 Protein”

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PubMed2006

Presence of serum tripartite motif-containing 21 antibodies in patients with esophageal squamous cell carcinoma.

SEREX has been applied to esophageal SCC, and the TRIM21 gene was identified as a novel SEREX antigen of esophageal SCC. The presence of s-TRIM21-Abs was confirmed by Western blotting using bacterially expressed TRIM21 gene product and was evaluated for clinicopathological significance in patients with esophageal SCC. s-TRIM21-Abs were detected in 18 (20%) of 91 patients with esophageal SCC but not in 42 healthy donors. The presence of s-TRIM21-Abs was partly associated with tumor size (P = 0.063) and poor survival (P = 0.067). To measure serum antibody levels, ELISA using purified recombinant TRIM21 protein was developed. The levels of s-TRIM21-Abs were significantly higher in patients with esophageal SCC than in healthy donors (P = 0.013). s-TRIM21-Abs may be a useful tumor marker to diagnose and predict disease progression in patients with esophageal SCC.

Adult↗

PubMed2006

TRIM21 is a trimeric protein that binds IgG Fc via the B30.2 domain.

TRIMs comprise a large protein family that include anti-retroviral restriction factors such as TRIM5alpha. Auto-antibodies to TRIM21 (Ro52) are a common serological feature of patients with Sjogren's syndrome and systemic lupus erythematosus (SLE). We show that, in addition to this autoantibody response, TRIM21 binds specifically to the Fc region of human IgG isotypes 1, 2 and 4, via a conformation dependent interaction. The minimal binding epitope was identified as the C-terminal B30.2 domain. The interaction was independent of N-linked glycosylation of the IgG CH2 domain. TRIM21 formed a trimer that competed with protein A for binding to IgG Fc. We conclude that TRIM21 binds to the consensus CH2/CH3 domain interface in the Fc region, overlapping the binding site of several other proteins, including Staphylococcus aureus protein A and Streptococcus spp. protein G. The data suggest that the normal function of TRIM21 involves regulation of IgG functions and that TRIM/B30.2 molecules may have broader and unsuspected roles in innate immunity, beyond that of retroviral restriction.

Animals↗

PubMed2006

Functional replacement of the RING, B-box 2, and coiled-coil domains of tripartite motif 5alpha (TRIM5alpha) by heterologous TRIM domains.

Tripartite motif 5alpha (TRIM5alpha) restricts some retroviruses, including human immunodeficiency virus type 1 (HIV-1), from infecting the cells of particular species. TRIM5alpha is a member of the TRIM family of proteins, which contain RING, B-box, coiled-coil (CC), and, in some cases, B30.2(SPRY) domains. Here we investigated the abilities of domains from TRIM proteins (TRIM6, TRIM34, and TRIM21) that do not restrict HIV-1 infection to substitute for the domains of rhesus monkey TRIM5alpha (TRIM5alpha(rh)). The RING, B-box 2, and CC domains of the paralogous TRIM6 and TRIM34 proteins functionally replaced the corresponding TRIM5alpha(rh) domains, allowing HIV-1 restriction. By contrast, similar chimeras containing the components of TRIM21, a slightly more distant relative of TRIM5, did not restrict HIV-1 infection. The TRIM21 B-box 2 domain and its flanking linker regions contributed to the functional defectiveness of these chimeras. All of the chimeric proteins formed trimers. All of the chimeras that restricted HIV-1 infection bound the assembled HIV-1 capsid complexes. These results indicate that heterologous RING, B-box 2, and CC domains from related TRIM proteins can functionally substitute for TRIM5alpha(rh) domains.

Amino Acid Motifs↗

PubMed2026

TRIM21 induces selective autophagy of viruses and bacteria.

TRIM21 is an exceptionally versatile ubiquitin ligase that can be directed by antibodies to target oligomeric protein scaffolds, viral capsids, and proteopathic aggregates for intracellular degradation. How the cell degrades these typically resistant substrates remains poorly understood. To address this, we used TRIM21 viral restriction to create a genome-wide phenotypic screen for antibody-dependent capsid degradation. We identify an antimicrobial selective macroautophagy pathway in mammalian cells, which we term "antibody-directed xenophagy" (ADX). We show that this mechanism restricts structurally diverse pathogens, including adenovirus and Salmonella. Using quantitative microscopy, we demonstrate that TRIM21 rapidly intercepts antibody-pathogen complexes, leading to ubiquitin ligase activation. Following this, selective autophagy adaptors are recruited, and viral cargoes are delivered to lysosomes. This process reduces Salmonella pathology and bacterial tissue invasion in mice. We propose that TRIM21 evolved through competition with pathogens to induce autophagy of diverse and complex substrates, potentially explaining its versatility for targeted protein degradation.

TRIM21 Protein↗

PubMed2026

Immunoproteomic Profiling of Autoantibodies and Antibodies against Infectious Agents in Autoimmune Diseases.

Prior research investigated limited antibody sets within individual autoimmune diseases. Using the Nucleic-Acid Programmable Protein Array platform, we measured antibodies against 280 human, 40 viral, and 15 bacterial antigens in serum from 237 patients with 8 autoimmune diseases, including autoimmune gastritis (AG), autoimmune thyroiditis (AT), celiac disease (CD), idiopathic inflammatory myopathies (IIM), type 1 diabetes mellitus (T1D), rheumatoid arthritis (RA), Sjögren's disease (SjD), and systemic lupus erythematosus (SLE), and 112 controls. Candidate antibodies were identified by combining Firth logistic regression and machine learning. We identified disease-specific antibodies, ranging from 3 in IIM to 13 in SLE for IgG and 1 in CD to 13 in AG for IgA. Additionally, 63 IgG and 44 IgA antibodies were shared across two or more diseases. Notably, two IgG autoantibodies overlapped in up to five diseases: directed against STNM4 (SLE, SjD, T1D, CD, and RA) and TRIM21 (SLE, SjD, IIM, CD, and RA); and three IgA antibodies in up to seven diseases: directed against H1N1 Influenza A virus NP (IIM, SjD, AG, T1D, CD, RA, and AT) and Coxsackievirus B3MK012537 and Enterovirus C PVgp1 (IIM, SjD, AG, T1D, CD, SLE, and RA). These findings underscore the potential of antibody profiling in autoimmune disease characterization and biomarker discovery.

Humans↗

PubMed2006

Rapid turnover and polyubiquitylation of the retroviral restriction factor TRIM5.

TRIM5alpha and TRIMCyp are retroviral restriction factors that, like other members of the tripartite motif (TRIM) family, contain RING, B-box 2 and coiled-coil domains. We found that both proteins are rapidly turned over, with half-lives of 50-60 min. Polyubiquitylation and rapid degradation of TRIM5alpha depended upon intact RING and B-box 2 domains. A chimera consisting of monkey TRIM5alpha with a RING domain of human TRIM21 exhibited a half-life of 210 min, yet potently restricted human immunodeficiency virus; therefore, rapid turnover of TRIM5alpha is not required for its antiretroviral activity. TRIM5alpha forms cytoplasmic bodies that contain other polyubiquitylated proteins, heat shock proteins and dynein, and thus resemble aggresome precursors. Consistent with this interpretation, proteasomal inhibitors triggered the formation of TRIM5alpha(rh)-containing aggresomes in a microtubule-dependent manner. Thus, TRIM5alpha levels in the cell are maintained by continuous synthesis and rapid proteasome-mediated degradation, imbalances in which result in the formation of pre-aggresomal cytoplasmic bodies.

Antiviral Restriction Factors↗