TRAF3
TRAF3 (TNF receptor-associated factor 3) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Multiple myeloma.
Overview
Cytoplasmic E3 ubiquitin ligase that regulates various signalling pathways, such as the NF-kappa-B, mitogen-activated protein kinase (MAPK) and interferon regulatory factor (IRF) pathways, and thus controls a lot of biological processes in both immune and non-immune cell types. In TLR and RLR signalling pathways, acts as an E3 ubiquitin ligase promoting the synthesis of 'Lys-63'-linked polyubiquitin chains on several substrates such as ASC that lead to the activation of the type I interferon response or the inflammasome. Following the activation of certain TLRs such as TLR4, acts as a negative NF-kappa-B regulator, possibly to avoid unregulated inflammatory response, and its degradation via 'Lys-48'-linked polyubiquitination is required for MAPK activation and production of inflammatory cytokines.
IntOGen calls it a driver in 1 cohort (0 activating, 1 loss-of-function), covering Plasma Cell Myeloma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · TRAF3 (TNF receptor-associated factor 3) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Multiple myeloma.
- 1 · What it is
TRAF3 (TNF receptor-associated factor 3) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Multiple myeloma.
- 2 · What goes wrong in cancer
Cytoplasmic E3 ubiquitin ligase that regulates various signalling pathways, such as the NF-kappa-B, mitogen-activated protein kinase (MAPK) and interferon regulatory factor (IRF) pathways, and thus controls a lot of biological processes in both immune and non-immune cell types.
- 3 · How drugs use it
No product in this corpus aims at TRAF3 yet. Because the protein is lost rather than overactive, drugs either restore its function or exploit the weakness its loss leaves (synthetic lethality).
External identifiers
Sources: HGNC HGNC:12033 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q13114 (protein name, function text, keywords and locations (REST API)); IntOGen TRAF3 (driver in 1 cohort (Act 0, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Cytoplasmic E3 ubiquitin ligase that regulates various signalling pathways, such as the NF-kappa-B, mitogen-activated protein kinase (MAPK) and interferon regulatory factor (IRF) pathways, and thus controls a lot of biological processes in both immune and non-immune cell types. In TLR and RLR signalling pathways, acts as an E3 ubiquitin ligase promoting the synthesis of 'Lys-63'-linked polyubiquitin chains on several substrates such as ASC that lead to the activation of the type I interferon response or the inflammasome. Following the activation of certain TLRs such as TLR4, acts as a negative NF-kappa-B regulator, possibly to avoid unregulated inflammatory response, and its degradation via 'Lys-48'-linked polyubiquitination is required for MAPK activation and production of inflammatory cytokines. Alternatively, when TLR4 orchestrates bacterial expulsion, TRAF3 undergoes 'Lys-33'-linked polyubiquitination and subsequently binds to RALGDS, mobilising the exocyst complex to rapidly expel intracellular bacteria back for clearance. Also acts as a constitutive negative regulator of the alternative NF-kappa-B pathway, which controls B-cell survival and lymphoid organ development. Required for normal antibody isotype switching from IgM to IgG. Location: Cytoplasm; Endosome; Mitochondrion (UniProt). Locus 14q32.32 (HGNC).
- Multiple myeloma: IntOGen driver in 1 cohort (PCM)
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it a loss-of-function (LoF) driver in 1 cohort. Evidence tier "cohort-driver" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery for this target: (TITLE:"TRAF3" OR ABSTRACT:"TRAF3" OR TITLE:"TNF receptor associated factor 3" OR ABSTRACT:"TNF receptor associated factor 3" OR TITLE:"TNF receptor-associated factor 3" OR ABSTRACT:"TNF receptor-associated factor 3" OR TITLE:"CAP-1" OR ABSTRACT:"CAP-1" OR TITLE:"CD40bp" OR ABSTRACT:"CD40bp" OR TITLE:"CRAF1" OR ABSTRACT:"CRAF1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about TRAF3, not a curated reading list.