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Transient deSUMOylation of IRF2BP proteins controls early transcription in EGFR signaling
Author(s) -
Barysch Sina V,
StankovicValentin Nicolas,
Miedema Tim,
Karaca Samir,
Doppel Judith,
Nait Achour Thiziri,
Vasudeva Aarushi,
Wolf Lucie,
Sticht Carsten,
Urlaub Henning,
Melchior Frauke
Publication year - 2021
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201949651
Subject(s) - sumo protein , transcription factor , biology , microbiology and biotechnology , signal transduction , transcription (linguistics) , proteome , ubiquitin , gene , genetics , linguistics , philosophy
Molecular switches are essential modules in signaling networks and transcriptional reprogramming. Here, we describe a role for small ubiquitin‐related modifier SUMO as a molecular switch in epidermal growth factor receptor (EGFR) signaling. Using quantitative mass spectrometry, we compare the endogenous SUMO proteomes of HeLa cells before and after EGF stimulation. Thereby, we identify a small group of transcriptional coregulators including IRF2BP1, IRF2BP2, and IRF2BPL as novel players in EGFR signaling. Comparison of cells expressing wild type or SUMOylation‐deficient IRF2BP1 indicates that transient deSUMOylation of IRF2BP proteins is important for appropriate expression of immediate early genes including dual specificity phosphatase 1 (DUSP1, MKP‐1) and the transcription factor ATF3. We find that IRF2BP1 is a repressor, whose transient deSUMOylation on the DUSP1 promoter allows—and whose timely reSUMOylation restricts—DUSP1 transcription. Our work thus provides a paradigm how comparative SUMO proteome analyses serve to reveal novel regulators in signal transduction and transcription.