TRAF6 and A20 Regulate Lysine 63–Linked Ubiquitination of Beclin-1 to Control TLR4-Induced Autophagy

@article{Shi2010TRAF6AA,
  title={TRAF6 and A20 Regulate Lysine 63–Linked Ubiquitination of Beclin-1 to Control TLR4-Induced Autophagy},
  author={C. Shi and J. Kehrl},
  journal={Science Signaling},
  year={2010},
  volume={3},
  pages={ra42 - ra42}
}
Regulation of the ubiquitination of Beclin-1 may be a general mechanism that controls autophagy. Controlling the Inner Pac-Man Autophagy is a process by which cellular components can be recycled to provide much-needed raw materials to help cells survive conditions of acute stress. But if a cell has to rely on this process for too long, the cell will die. TLR4 is a receptor that responds to a bacterial component called LPS to activate the transcription factor NF-κB, which drives the expression… Expand
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References

SHOWING 1-10 OF 46 REFERENCES
The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses
TLDR
A20 was required for the termination of Toll-like receptor–induced activity of the transcription factor NF-κB and proinflammatory gene expression in macrophages, and this function protected mice from endotoxic shock, indicating that A20 is also critical for the regulation of TNF-independent signals in vivo. Expand
MyD88 and Trif Target Beclin 1 to Trigger Autophagy in Macrophages*
TLDR
It is demonstrated that not only TLR4, but also other TLR family members induce autophagy in macrophages, which is inhibited by MyD88, Trif, or Beclin 1 shRNA expression. Expand
De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-κB signalling
TLDR
A novel ubiquitin ligase domain is defined and two sequential mechanisms by which A20 downregulates NF-κB signalling are identified, both of which participate in mediating a distinct regulatory effect. Expand
CD40-TRAF6 and Autophagy-Dependant Anti-Microbial Activity in Macrophages
TLDR
It is reported that vacuole-lysosome fusion is dependent on synergy between TRAF6 signaling downstream of CD40 and TNF-alpha, which identified a new paradigm by which T cells eradicate an intracellular pathogen within macrophages. Expand
Cutting Edge: Autoantigen Ro52 Is an Interferon Inducible E3 Ligase That Ubiquitinates IRF-8 and Enhances Cytokine Expression in Macrophages1
TLDR
Together, Ro52 is an E3 ligase for IRF-8 that acts in a non-degradation pathway of ubiquitination, and contributes to the elicitation of innate immunity in macrophages. Expand
Autophagy genes in immunity
TLDR
Phenotypes that result from the inactivation of autophagy genes in the immune system are summarized and the pleiotropic functions of autophile genes in immunity are discussed. Expand
Trabid, a new positive regulator of Wnt-induced transcription with preference for binding and cleaving K63-linked ubiquitin chains.
TLDR
Trabid is identified as a new positive regulator of Wnt signaling in mammalian and Drosophila cells and its activities are required for efficient TCF-mediated transcription in cells with high Wnt pathway activity, including colorectal cancer cell lines. Expand
Toll-like receptor 4 is a sensor for autophagy associated with innate immunity.
TLDR
It is shown that Toll-like receptor 4 (TLR4) served as a previously unrecognized environmental sensor for autophagy, and a new molecular pathway in which LPS-induced Autophagy was regulated through a Toll-interleukin-1 receptor domain-containing adaptor-inducing interferon-beta (TRIF)-dependent, myeloid differentiation factor 88 (MyD88)-independent TLR4 signaling pathway was defined. Expand
Bcl-2 Antiapoptotic Proteins Inhibit Beclin 1-Dependent Autophagy
TLDR
Bcl-2 not only functions as an antiapoptotic protein, but also as an antiautophagy protein via its inhibitory interaction with Beclin 1, which may help maintain autophagy at levels that are compatible with cell survival, rather than cell death. Expand
Crystal Structure of the Bcl-XL-Beclin 1 Peptide Complex
TLDR
It is reported that Beclin 1 contains a conserved BH3 domain, which is both necessary and sufficient for its interaction with Bcl-XL, and proposed that this putative apoptotic function may be linked to the ability of BeClin 1 to suppress tumor formation in mammals. Expand
...
1
2
3
4
5
...