Substrates of the ASB2α E3 ubiquitin ligase in dendritic cells

Conventional dendritic cells (cDCs) comprise distinct populations with specialized immune functions that are mediators of innate and adaptive immune responses. Transcriptomic and proteomic approaches have been used so far to identify transcripts and proteins that are differentially expressed in thes...

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Bibliographic Details
Published in:Scientific reports 2015-11, Vol.5 (1), p.16269-16269, Article 16269
Main Authors: Spinner, Camille A., Uttenweiler-Joseph, Sandrine, Metais, Arnaud, Stella, Alexandre, Burlet-Schiltz, Odile, Moog-Lutz, Christel, Lamsoul, Isabelle, Lutz, Pierre G.
Format: Article
Language:English
Subjects:
13/51
14/63
38/77
631/250/2504/133
631/337/474/2073
64/60
82/58
Adaptor Proteins, Signal Transducing - metabolism
Animals
Biochemistry, Molecular Biology
Cell Line, Tumor
Cellular Biology
Dendritic Cells - metabolism
Filamins - metabolism
HeLa Cells
Humanities and Social Sciences
Humans
Life Sciences
Mice
Mice, Knockout
multidisciplinary
Proteasome Endopeptidase Complex - metabolism
Proteomics - methods
Science
Ubiquitin - metabolism
Ubiquitin-Protein Ligases - metabolism
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Summary:Conventional dendritic cells (cDCs) comprise distinct populations with specialized immune functions that are mediators of innate and adaptive immune responses. Transcriptomic and proteomic approaches have been used so far to identify transcripts and proteins that are differentially expressed in these subsets to understand the respective functions of cDCs subsets. Here, we showed that the Cullin 5-RING E3 ubiquitin ligase (E3) ASB2α, by driving degradation of filamin A (FLNa) and filamin B (FLNb), is responsible for the difference in FLNa and FLNb abundance in the different spleen cDC subsets. Importantly, the ability of these cDC subsets to migrate correlates with the level of FLNa. Furthermore, our results strongly point to CD4 positive and double negative cDCs as distinct populations. Finally, we develop quantitative global proteomic approaches to identify ASB2α substrates in DCs using ASB2 conditional knockout mice. As component of the ubiquitin-proteasome system (UPS) are amenable to pharmacological manipulation, these approaches aimed to the identification of E3 substrates in physiological relevant settings could potentially lead to novel targets for therapeutic strategies.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep16269