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Cell Rep DOI:10.1016/j.celrep.2016.11.005

RNF166 Determines Recruitment of Adaptor Proteins during Antibacterial Autophagy.

Publication TypeJournal Article
Year of Publication2016
AuthorsHeath, RJ, Goel, G, Baxt, LA, Rush, JS, Mohanan, V, Paulus, GLC, Jani, V, Lassen, KG, Xavier, RJ
JournalCell Rep
Volume17
Issue9
Pages2183-2194
Date Published2016 11 22
ISSN2211-1247
KeywordsAdaptor Proteins, Signal Transducing, Anti-Bacterial Agents, Autophagy, HEK293 Cells, HeLa Cells, Humans, Listeria, Lysine, Protein Binding, RNA, Small Interfering, Salmonella typhimurium, Sequestosome-1 Protein, Ubiquitin-Protein Ligases, Ubiquitination
Abstract

Xenophagy is a form of selective autophagy that involves the targeting and elimination of intracellular pathogens through several recognition, recruitment, and ubiquitination events. E3 ubiquitin ligases control substrate selectivity in the ubiquitination cascade; however, systematic approaches to map the role of E3 ligases in antibacterial autophagy have been lacking. We screened more than 600 putative human E3 ligases, identifying E3 ligases that are required for adaptor protein recruitment and LC3-bacteria colocalization, critical steps in antibacterial autophagy. An unbiased informatics approach pinpointed RNF166 as a key gene that interacts with the autophagy network and controls the recruitment of ubiquitin as well as the autophagy adaptors p62 and NDP52 to bacteria. Mechanistic studies demonstrated that RNF166 catalyzes K29- and K33-linked polyubiquitination of p62 at residues K91 and K189. Thus, our study expands the catalog of E3 ligases that mediate antibacterial autophagy and identifies a critical role for RNF166 in this process.

DOI10.1016/j.celrep.2016.11.005
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/27880896?dopt=Abstract

Alternate JournalCell Rep
PubMed ID27880896
PubMed Central IDPMC5192565
Grant ListP30 DK043351 / DK / NIDDK NIH HHS / United States
R01 DK097485 / DK / NIDDK NIH HHS / United States
U19 AI109725 / AI / NIAID NIH HHS / United States