PMID:23148214

Citation	'Abdulrahman, BB, Abu Khweek, A, Akhter, A, Caution, K, Tazi, M, Hassan, H, Zhang, Y, Rowland, PD, Malhotra, S, Aeffner, F, Davis, IC, Valvano, MA and Amer, AO (2012) Depletion of the ubiquitin binding adaptor molecule SQSTM1/p62 from macrophages harboring cftr {Delta}F508 mutation improves the delivery of Burkholderia cenocepacia to the autophagic machinery. J. Biol. Chem. '
Abstract	Cystic fibrosis (CF) is the most common inherited lethal disease in Caucasians. It is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) of which the cftr ΔF508 mutation is the most common. ΔF508 macrophages are intrinsically defective in autophagy due to the sequestration of essential autophagy molecules within unprocessed CFTR aggregates. Defective autophagy allows Burkholderia cenocepacia (B. cepacia) to survive and replicate in ΔF508 macrophages. Infection by B. cepacia poses great risk to CF patients because it causes accelerated lung inflammation and in some cases a lethal necrotizing pneumonia. Autophagy is a cell survival mechanism whereby an autophagosome engulfs non-functional organelles and delivers them to the lysosome for degradation. The ubiquitin binding adaptor protein SQSTM1/p62 is required for the delivery of several ubiquitinated cargos to the autophagosome. In wild-type (WT) macrophages, p62 depletion and overexpression lead to increased and decreased bacterial intracellular survival, respectively. In contrast, depletion of p62 in ΔF508 macrophages results in decreased bacterial survival, whereas overexpression of p62 leads to increased B. cepacia intracellular growth. Interestingly, the depletion of p62 from ΔF508 macrophages results in the release of the autophagy molecule beclin1 (BECN1), from the mutant CFTR aggregates and allows its redistribution and recruitment to the B. cepacia vacuole, mediating the acquisition of the autophagy marker LC3 and bacterial clearance via autophagy. These data demonstrate that p62 differentially dictates the fate of B. cepacia infection in WT and F508 macrophages.
Links	PubMed Online version:10.1074/jbc.M112.411728
Keywords
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:SQSTM		GO:0044130: negative regulation of growth of symbiont in host	ECO:0000315:		P		FIGURE 4, 5	complete CACAO 5860
MOUSE:SQSTM	involved_in	GO:0044130: negative regulation of growth of symbiont in host	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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