Quantitative analysis of the TNF-α-induced phosphoproteome reveals AEG-1/MTDH/LYRIC as an IKKβ substrate

摘要: The inhibitor of the nuclear factor-κB (IκB) kinase (IKK) complex is a key regulator canonical NF-κB signalling cascade and crucial for fundamental cellular functions, including stress immune responses. majority IKK functions are attributed to activation; however, there increasing evidence pathway-independent signalling. Here we combine quantitative mass spectrometry with random forest bioinformatics dissect TNF-α-IKKβ-induced phosphoproteome in MCF-7 breast cancer cells. In total, identify over 20,000 phosphorylation sites, which ∼1% regulated up on TNF-α stimulation. We various potential novel IKKβ substrates kinases regulators trafficking. Moreover, show that one candidates, AEG-1/MTDH/LYRIC, directly phosphorylated by serine 298. provide IKKβ-mediated AEG-1 essential IκBα degradation as well NF-κB-dependent gene expression cell proliferation, correlate patient survival vivo.