title: Substrates of the ASB2α E3 ubiquitin ligase in dendritic cells.
abstract: 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.
authors.affiliation: CNRS; IPBS (Institut de Pharmacologie et de Biologie Structurale); 205 route de Narbonne BP 64182, F-31077 Toulouse, France.|Université de Toulouse, UPS, IPBS, F-31077 Toulouse, France.
authors.forename: Camille A
authors.initials: CA
authors.lastname: Spinner
authors.affiliation: CNRS; IPBS (Institut de Pharmacologie et de Biologie Structurale); 205 route de Narbonne BP 64182, F-31077 Toulouse, France.|Université de Toulouse, UPS, IPBS, F-31077 Toulouse, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Uttenweiler-Joseph
authors.affiliation: CNRS; IPBS (Institut de Pharmacologie et de Biologie Structurale); 205 route de Narbonne BP 64182, F-31077 Toulouse, France.|Université de Toulouse, UPS, IPBS, F-31077 Toulouse, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Metais
authors.affiliation: CNRS; IPBS (Institut de Pharmacologie et de Biologie Structurale); 205 route de Narbonne BP 64182, F-31077 Toulouse, France.|Université de Toulouse, UPS, IPBS, F-31077 Toulouse, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Stella
authors.affiliation: CNRS; IPBS (Institut de Pharmacologie et de Biologie Structurale); 205 route de Narbonne BP 64182, F-31077 Toulouse, France.|Université de Toulouse, UPS, IPBS, F-31077 Toulouse, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Burlet-Schiltz
authors.affiliation: CNRS; IPBS (Institut de Pharmacologie et de Biologie Structurale); 205 route de Narbonne BP 64182, F-31077 Toulouse, France.|Université de Toulouse, UPS, IPBS, F-31077 Toulouse, France.
authors.forename: Christel
authors.initials: C
authors.lastname: Moog-Lutz
authors.affiliation: CNRS; IPBS (Institut de Pharmacologie et de Biologie Structurale); 205 route de Narbonne BP 64182, F-31077 Toulouse, France.|Université de Toulouse, UPS, IPBS, F-31077 Toulouse, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Lamsoul
authors.affiliation: CNRS; IPBS (Institut de Pharmacologie et de Biologie Structurale); 205 route de Narbonne BP 64182, F-31077 Toulouse, France.|Université de Toulouse, UPS, IPBS, F-31077 Toulouse, France.
authors.forename: Pierre G
authors.initials: PG
authors.lastname: Lutz
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000378:metabolism*; D064448:Filamins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D050826:Suppressor of Cytokine Signaling Proteins; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C542087:Asb2 protein, mouse; D064448:Filamins; D050826:Suppressor of Cytokine Signaling Proteins; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex