Willmann, Katharina L; Sacco, RobertoISTA; Martins, Rui; Garncarz, Wojciech; Krolo, Ana; Knapp, Sylvia; Bennett, Keiryn L; Boztug, Kaan
NF-κB signaling is a central pathway of immunity and integrates signal transduction upon a wide array of inflammatory stimuli. Noncanonical NF-κB signaling is activated by a small subset of TNF family receptors and characterized by NF-κB2/p52 transcriptional activity. The medical relevance of this pathway has recently re-emerged from the discovery of primary immunodeficiency patients that have loss-of-function mutations in the MAP3K14 gene encoding NIK. Nevertheless, knowledge of protein interactions that regulate noncanonical NF-κB signaling is sparse. Here we report a detailed state-of-the-art mass spectrometry-based protein–protein interaction network including the noncanonical NF-κB signaling nodes TRAF2, TRAF3, IKKα, NIK, and NF-κB2/p100. The value of the data set was confirmed by the identification of interactions already known to regulate this pathway. In addition, a remarkable number of novel interactors were identified. We provide validation of the novel NIK and IKKα interactor FKBP8, which may regulate processes downstream of noncanonical NF-κB signaling. To understand perturbed noncanonical NF-κB signaling in the context of misregulated NIK in disease, we also provide a differential interactome of NIK mutants that cause immunodeficiency. Altogether, this data set not only provides critical insight into how protein–protein interactions can regulate immune signaling but also offers a novel resource on noncanonical NF-κB signaling.
Journal of Proteome Research
Austrian Science Fund (FWF) Lise Meitner Program Fellowship (FWF M-1809, to K.L.W.), FWF Infect-ERA framework (I-1620_B22, to S.K.), European Research Council (ERC StG 310857, to K.B.) We thank Jacques Colinge, André C. Müller, and Peter Májek for fruitful discussions and Elisabeth Salzer and Kate G. Ackermann for critically reading the manuscript. We thank Giulio Superti-Furga for providing pTO-SII-HA-GW plasmids.
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Willmann K, Sacco R, Martins R, et al. Expanding the interactome of the noncanonical NF-κB signaling pathway. Journal of Proteome Research. 2016;15(9):2900-2909. doi:10.1021/acs.jproteome.5b01004
Willmann, K., Sacco, R., Martins, R., Garncarz, W., Krolo, A., Knapp, S., … Boztug, K. (2016). Expanding the interactome of the noncanonical NF-κB signaling pathway. Journal of Proteome Research. American Chemical Society. https://doi.org/10.1021/acs.jproteome.5b01004
Willmann, Katharina, Roberto Sacco, Rui Martins, Wojciech Garncarz, Ana Krolo, Sylvia Knapp, Keiryn Bennett, and Kaan Boztug. “Expanding the Interactome of the Noncanonical NF-ΚB Signaling Pathway.” Journal of Proteome Research. American Chemical Society, 2016. https://doi.org/10.1021/acs.jproteome.5b01004.
K. Willmann et al., “Expanding the interactome of the noncanonical NF-κB signaling pathway,” Journal of Proteome Research, vol. 15, no. 9. American Chemical Society, pp. 2900–2909, 2016.
Willmann K, Sacco R, Martins R, Garncarz W, Krolo A, Knapp S, Bennett K, Boztug K. 2016. Expanding the interactome of the noncanonical NF-κB signaling pathway. Journal of Proteome Research. 15(9), 2900–2909.
Willmann, Katharina, et al. “Expanding the Interactome of the Noncanonical NF-ΚB Signaling Pathway.” Journal of Proteome Research, vol. 15, no. 9, American Chemical Society, 2016, pp. 2900–09, doi:10.1021/acs.jproteome.5b01004.
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