ArticleMolecular and cellular biology2010
RSK-mediated phosphorylation in the C/EBP{beta} leucine zipper regulates DNA binding, dimerization, and growth arrest activity.
Article in Molecular and cellular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 83 citations in OpenAlex.
- 3'UTR-directed, kinase-proximal mRNA decay inhibits C/EBPβ phosphorylation/activation to suppress senescence in tumor cells.iScience · 2026Article
- The transcription factor C/EBPβ promotes hyperglycemia-elicited glycolysis and liver cancer progression.Nature communications · 2026Article
- C/EBPγ induces epithelial-mesenchymal transition and facilitates DNA double-strand break repair in lung adenocarcinoma cells.Cell death discovery · 2026Article
- Comprehensive Genome-Wide Investigation and Transcriptional Regulation of the bZIP Gene Family in Litchi Fruit Development.Plants (Basel, Switzerland) · 2025Article
- Mst1-mediated phosphorylation of FoxO1 and C/EBP-β stimulates cell-protective mechanisms in cardiomyocytes.Nature communications · 2024Article
- IGF2 deficiency promotes liver aging through mitochondrial dysfunction and upregulated CEBPB signaling in D-galactose-induced aging mice.Molecular medicine (Cambridge, Mass.) · 2023Article
- Normal cell cycle progression requires negative regulation of E2F1 by Groucho during S phase and its relief at G2 phase.Development (Cambridge, England) · 2023Article
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- Multi-omics analysis of an in vitro photoaging model and protective effect of umbilical cord mesenchymal stem cell-conditioned medium.Stem cell research & therapy · 2022Article
- Combination of midostaurin and ATRA exerts dose-dependent dual effects on acute myeloid leukemia cells with wild type FLT3.BMC cancer · 2022Article
- Long term therapeutic effects of icariin-loaded PLGA microspheres in an experimental model of optic nerve ischemia via modulation of CEBP-β/G-CSF/noncanonical NF-κB axis.Bioengineering & translational medicine · 2022Article
- CCAAT enhancer binding protein gamma (C/EBP-γ): An understudied transcription factor.Advances in biological regulation · 2022Review
- The "Janus" Role of C/EBPs Family Members in Cancer Progression.International journal of molecular sciences · 2020Review
- Characterization of bZIP transcription factors fromJournal of genetics · 2020Article
- Enzastaurin enhances ATRA-induced differentiation of acute myeloid leukemia cells.American journal of translational research · 2020Article
- OsbZIP42 is a positive regulator of ABA signaling and confers drought tolerance to rice.Planta · 2019Article
- Article
- Remifentanil upregulates hepatic IL-18 binding protein (IL-18BP) expression through transcriptional control.Laboratory investigation; a journal of technical methods and pathology · 2018Article
- A RAS-CaMKKβ-AMPKα2 pathway promotes senescence by licensing post-translational activation of C/EBPβ through a novel 3'UTR mechanism.Oncogene · 2018Article
- The C/EBPβ LIP isoform rescues loss of C/EBPβ function in the mouse.Scientific reports · 2018Article
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
The bZIP transcription factor C/EBPbeta is a target of Ras signaling that has been implicated in Ras-induced transformation and oncogene-induced senescence (OIS). To gain insights into Ras-C/EBPbeta signaling, we investigated C/EBPbeta activation by oncogenic Ras. We show that C/EBPbeta DNA binding is autorepressed and becomes activated by the Ras-Raf-MEK-ERK-p90(RSK) cascade. Inducible phosphorylation by RSK on Ser273 in the leucine zipper was required for DNA binding. In addition, three other modifications (phosphorylation on Tyr109 [p-Tyr109], p-Ser111, and monomethylation of Arg114 [me-Arg114]) within an N-terminal autoinhibitory domain were important for Ras-induced C/EBPbeta activation and cytostatic activity. Apart from its role in DNA binding, Ser273 phosphorylation also creates an interhelical g<-->e' salt bridge with Lys268 that increases attractive electrostatic interactions between paired leucine zippers and promotes homodimerization. Mutating Ser273 to Ala or Lys268 to Glu decreased C/EBPbeta homodimer formation, whereas heterodimerization with C/EBPgamma was relatively unaffected. The S273A substitution also reduced the antiproliferative activity of C/EBPbeta in Ras(V12)-expressing fibroblasts and decreased binding to target cell cycle genes, while a phosphomimetic substitution (S273D) maintained growth arrest function. Our findings identify four novel C/EBPbeta-activating modifications, including RSK-mediated phosphorylation of a bifunctional residue in the leucine zipper that regulates DNA binding and homodimerization and thereby promotes cell cycle arrest.
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