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An siRNA screen for ATG protein depletion reveals the extent of the unconventional functions of the autophagy proteome in virus replicationUnconventional functions of ATG proteins

Journal of Cell Biology, Rockefeller University Press, ISSN 1540-8140

Volume 214, 5, 2016

DOI:10.1083/jcb.201602046, Dimensions: pub.1039635206, PMC: PMC5004442, PMID: 27573464,

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  1. (1) Department of Cell Biology, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, Netherlands
  2. (2) University Medical Center Utrecht, grid.7692.a
  3. (3) Utrecht University, grid.5477.1
  4. (4) Goethe University Frankfurt, grid.7839.5
  5. (5) Northeast Agricultural University, grid.412243.2
  6. (6) The Francis Crick Institute, grid.451388.3
  7. (7) Heinrich Heine University Düsseldorf, grid.411327.2
  8. (8) Aarhus University, grid.7048.b, AU
  9. (9) University of Helsinki, grid.7737.4
  10. (10) Wilhelmina Children's Hospital, grid.417100.3

Description

Autophagy is a catabolic process regulated by the orchestrated action of the autophagy-related (ATG) proteins. Recent work indicates that some of the ATG proteins also have autophagy-independent roles. Using an unbiased siRNA screen approach, we explored the extent of these unconventional functions of ATG proteins. We determined the effects of the depletion of each ATG proteome component on the replication of six different viruses. Our screen reveals that up to 36% of the ATG proteins significantly alter the replication of at least one virus in an unconventional fashion. Detailed analysis of two candidates revealed an undocumented role for ATG13 and FIP200 in picornavirus replication that is independent of their function in autophagy as part of the ULK complex. The high numbers of unveiled ATG gene-specific and pathogen-specific functions of the ATG proteins calls for caution in the interpretation of data, which rely solely on the depletion of a single ATG protein to specifically ablate autophagy.

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Times Cited: 32

Field Citation Ratio (FCR): 5.16

Relative Citation ratio (RCR): 1.72

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