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Published on: September 7, 2018
Roles of tumor necrosis factor receptor associated factor 3 (TRAF3) and TRAF5 in immune cell functions
Joanne M Hildebrand1, Zuoan Yi, Claire M Buchta
1Department of Microbiology, The University of Iowa, Iowa City, IA 52242, USA.
Abstract:
A large and diverse group of receptors utilizes the family of cytoplasmic signaling proteins known as tumor necrosis factor receptor (TNFR)-associated factors (TRAFs). In recent years, there has been a resurgence of interest and exploration of the roles played by TRAF3 and TRAF5 in cellular regulation, particularly in cells of the immune system, the cell types of focus in this review. This work has revealed that TRAF3 and TRAF5 can play diverse roles for different receptors even in the same cell type, as well as distinct roles in different cell types. Evidence indicates that TRAF3 and TRAF5 play important roles beyond the TNFR-superfamily (SF) and viral mimics of its members, mediating certain innate immune receptor and cytokine receptor signals, and most recently, signals delivered by the T-cell receptor (TCR) signaling complex. Additionally, much research has demonstrated the importance of TRAF3-mediated cellular regulation via its cytoplasmic interactions with additional signaling proteins. In particular, we discuss below evidence for the participation by TRAF3 in a number of the regulatory post-translational modifications involving ubiquitin that are important in various signaling pathways.
Insights
Tumor necrosis factor receptor-associated factors (TRAFs), particularly TRAF3 and TRAF5, play diverse regulatory roles in immune cells. These proteins are crucial for various signaling pathways beyond the TNFR-superfamily, including innate immunity and T-cell receptor signaling.
Area of Science:
- Immunology
- Cellular Signaling
- Molecular Biology
Background:
- Tumor necrosis factor receptor (TNFR)-associated factors (TRAFs) are key cytoplasmic signaling proteins.
- TRAF3 and TRAF5 have garnered renewed interest for their roles in cellular regulation, especially within the immune system.
Purpose of the Study:
- To review the diverse and distinct roles of TRAF3 and TRAF5 in cellular regulation.
- To highlight their functions beyond the TNFR-superfamily, including innate immune and T-cell receptor signaling.
Main Methods:
- Literature review of recent research on TRAF3 and TRAF5 functions.
- Analysis of TRAF3 and TRAF5 involvement in various signaling pathways.
- Examination of TRAF3's role in ubiquitin-mediated post-translational modifications.
Main Results:
- TRAF3 and TRAF5 exhibit multifaceted roles, varying by receptor and cell type.
- These TRAFs are implicated in innate immune receptor, cytokine receptor, and T-cell receptor (TCR) signaling.
- TRAF3 participates in ubiquitin-mediated regulatory post-translational modifications crucial for signaling.
Conclusions:
- TRAF3 and TRAF5 are critical regulators in immune cell signaling with broad pathway involvement.
- Their functions extend beyond traditional TNFR-superfamily signaling, impacting innate and adaptive immunity.
- TRAF3's interactions and ubiquitin-modulating activities are central to cellular regulation.
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