The tumor necrosis factor receptor (TNF-R)-associated factor (TRAF) family of intracellular proteins were originally identified as signaling adaptors that bind directly to the cytoplasmic regions of receptors of the TNF-R superfamily. The past decade has witnessed rapid expansion of receptor families identified to employ TRAFs for signaling. These include Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I-like receptors (RLRs), T cell receptor, IL-1 receptor family, IL-17 receptors, IFN receptors and TGFβ receptors. In addition to their role as adaptor proteins, most TRAFs also act as E3 ubiquitin ligases to activate downstream signaling events. TRAF-dependent signaling pathways typically lead to the activation of nuclear factor-κBs (NF-κBs), mitogen-activated protein kinases (MAPKs), or interferon-regulatory factors (IRFs). Compelling evidence obtained from germ-line and cell-specific TRAF-deficient mice demonstrates that each TRAF plays indispensable and non-redundant physiological roles, regulating innate and adaptive immunity, embryonic development, tissue homeostasis, stress response, and bone metabolism. Notably, mounting evidence implicates TRAFs in the pathogenesis of human diseases such as cancers and autoimmune diseases, which has sparked new appreciation and interest in TRAF research. This review presents an overview of the current knowledge of TRAFs, with an emphasis on recent findings concerning TRAF molecules in signaling and in human diseases.
TRAF molecules in cell signaling and in human diseases
Published 2013 in Journal of Molecular Signaling
ABSTRACT
PUBLICATION RECORD
- Publication year
2013
- Venue
Journal of Molecular Signaling
- Publication date
2013-06-13
- Fields of study
Biology, Medicine
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
CITATION MAP
EXTRACTION MAP
CLAIMS
CONCEPTS
- autoimmune diseases
Immune-mediated diseases in which the body's immune system attacks self tissues and that are linked to TRAF biology here.
Aliases: autoimmune disease
- cancers
A class of human diseases characterized by malignant cell growth that the review links to TRAF research.
Aliases: cancer
- e3 ubiquitin ligase
An enzyme class that transfers ubiquitin to target proteins and is used by many TRAF members in signaling.
Aliases: ubiquitin ligase
- human diseases
Disease states in humans that are discussed as being associated with TRAF biology in the review.
Aliases: diseases in humans
- interferon-regulatory factors
A family of transcription factors involved in interferon-related signaling responses downstream of TRAFs.
Aliases: IRFs
- mapks
Mitogen-activated protein kinases that participate in TRAF-linked signaling cascades.
Aliases: mitogen-activated protein kinases
- nf-κbs
A family of transcription factors that are activated downstream of TRAF-linked signaling pathways.
Aliases: NF-kB, nuclear factor-κBs
- tnf-r superfamily
A superfamily of receptors that recruit TRAF proteins through their cytoplasmic regions to transmit signals.
Aliases: tumor necrosis factor receptor superfamily, TNF receptor superfamily
- traf-deficient mice
Mouse models with germ-line or cell-specific loss of TRAF genes used to define TRAF functions in physiology.
Aliases: TRAF knockout mice, TRAF-deficient mouse models
- traf family
A family of intracellular proteins that act as signaling adaptors and, for many members, ubiquitin ligases in receptor signaling pathways.
Aliases: TRAFs, tumor necrosis factor receptor-associated factor family