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Sci. Signal., 25 May 2010
Vol. 3, Issue 123, p. ra42
[DOI: 10.1126/scisignal.2000751]


Editor's Summary

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-{kappa}B, which drives the expression of pro-inflammatory genes in a process that requires a modifying enzyme called TRAF6 to switch on the pathway and an opposing enzyme called A20 to switch it off. Shi and Kehrl now show that these two enzymes play an analogous role in regulating TLR4-induced autophagy: TRAF6 modifies (ubiquitinates) a protein called Beclin-1, which initiates autophagy, whereas A20 counters the effects of TRAF6 and shuts the process down. The authors’ examination of other pro-autophagy pathways suggests that regulation of the ubiquitination state of Beclin-1 may be a general mechanism for the induction of autophagy by pro-inflammatory stimuli.

Citation: C. S. Shi, J. H. Kehrl, TRAF6 and A20 Regulate Lysine 63–Linked Ubiquitination of Beclin-1 to Control TLR4-Induced Autophagy. Sci. Signal. 3, ra42 (2010).

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