Two Beclin-1-interacting proteins, the run domain Beclin-1 interacting and cysteine-rich containing protein (Rubicon) and ATG14L, reciprocally regulate autophagy at different stages. Knockdown of Rubicon caused enhancement of autophagy while that of ATG14L caused a defect in autophagosome formation. Rubicon functions as part of a Beclin-1-PIK3C3-containing autophagy complex and is also an essential, positive regulator of the NAPDH oxidase complex. Upon microbial infection or TLR2 activation, Rubicon interacts with the CYBA subunit of the NAPDH oxidase complex, leading to a burst of reactive oxygen species and inflammatory cytokines.
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