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Free keywords:
ATF3; DUSP1; EGFR; IRF2BP1; SUMO
Abstract:
Molecular switches are essential modules in signaling networksand transcriptional reprogramming. Here, we describe a role forsmall ubiquitin-related modifier SUMO as a molecular switch inepidermal growth factor receptor (EGFR) signaling. Using quantita-tive mass spectrometry, we compare the endogenous SUMOproteomes of HeLa cells before and after EGF stimulation. Thereby,we identify a small group of transcriptional coregulators includingIRF2BP1, IRF2BP2, and IRF2BPL as novel players in EGFR signaling.Comparison of cells expressing wild type or SUMOylation-deficientIRF2BP1indicates that transient deSUMOylation of IRF2BP proteinsis important for appropriate expression of immediate early genesincludingdual specificity phosphatase1(DUSP1, MKP-1) and thetranscription factor ATF3. We find that IRF2BP1is a repressor,whose transient deSUMOylation on the DUSP1promoter allows—and whose timely reSUMOylation restricts—DUSP1transcription.Our work thus provides a paradigm how comparative SUMOproteome analyses serve to reveal novel regulators in signal trans-duction and transcription.
